СПОСОБ И УСТРОЙСТВО ДЛЯ ПРОГНОЗИРОВАНИЯ ЭФФЕКТИВНОЙ ДОЗЫ ИЛИ ВОСПРИИМЧИВОСТИ К 5-ГИДРОКСИ-1Н-ИМИДАЗОЛ-4-КАРБОКСАМИДУ, СПОСОБ ОПРЕДЕЛЕНИЯ КОЛИЧЕСТВА КСАНТОЗИНМОНОФОСФАТА, А ТАКЖЕ СРЕДСТВО И СПОСОБ ДЛЯ ЛЕЧЕНИЯ МИЕЛОДИСПЛАСТИЧЕСКОГО СИНДРОМА

СПОСОБЫ ОБНАРУЖЕНИЯ ФОЛАТНОГО РЕЦЕПТОРА 1 В ОБРАЗЦЕ ПАЦИЕНТА

ОЦЕНКА СТАБИЛЬНОСТИ БИОЛОГИЧЕСКОГО ПРЕПАРАТА В ПРЕДВАРИТЕЛЬНО ЗАПОЛНЕННЫХ ШПРИЦАХ

IDENTIFIZIERUNG VON AMINOSÄUREN DURCH MASSENSPEKTROMETRIE

Massenspektrometerinterfacegehäuse

Vorrichtung (100) zum Durchführen chemischer Analysen, wobei die Vorrichtung (100) umfasst: ein Massenspektrometriemodul (130) und ein Interfacemodul (120) in Kommunikation mit einem Eingang des Massenspektrometriemoduls (130), um Material, das eine Probeenthält, dem Massenspektrometriemodul (130) zuzuführen, wobei das Interfacemodul (120) umfasst: ein Behältnis (121), das eine Kammer (121A) definiert und eine Öffnung, um auf Komponenten zugreifen zu können, die in der Kammer (121A) angeordnet sind, eine Tür (122), um die Öffnung zu blockieren, wenn sich die Tür (122) in einer geschlossenen Position befindet, und um Zugriff auf die Kammer (121A) zu ermöglichen, wenn sich die Tür in einer geöffneten Position befindet, ein Dichtungselement (124) zum Anordnen zwischen der Tür (122) und dem Behältnis (121), um das Behältnis (121) abzudichten, wenn sich die Tür (122) in der geschlossenen Position befindet, wobei das Dichtungselement (124) einen modifizierten O-Ring umfasst, wobei der modifizierte ...

VERFAHREN UND VORRICHTUNG ZUR GEL-FREIEN QUALITATIVEN PROTEOMANALYSE UND DEREN VERWENDUNGEN

Elucidating the metabolism of substances, useful for investigating the degradation of pharmaceuticals, comprises analyzing substances in a liquid reaction system to identify the metabolites by liquid chromatography and mass spectrometry

Elucidating the metabolism of substances, comprising analyzing substances in a liquid reaction system to determine the decomposition product, is new. Elucidating the metabolism of substances, comprising analyzing substances in a liquid reaction system to determine the decomposition products, is new. Potential decomposition products are computed in advance according to a set of degrading rules matching the effects of enzymes, to set the conditions for identification in the analysis procedure. The analysis uses a combination of chromatography to separate the liquid components to be identified by mass spectrometry.

Mass spectrometer

Methods and systems for chromatography/mass-spectrometry analysis

Rapid analysis of steroids and steroid derivatives

The subject technology is directed to a CO2-based chromatography system and method for rapid determination of the levels and/or the presence or absence of steroids or steroid derivatives in a sample.

Method and apparatus for providing a substance for the analysis of isotope ratios

An interface probe

A gas chromatography interface probe 100 comprises a copper inner tube 104 in a heated transfer line. A stainless steel GC fitting (150, Fig 7) may be secured to a first end of the inner tube and may comprise a flat portion 153 so that the fitting moves linearly with respect to GC end cap 112. An analyser cap 110 comprising a non-planar wall may be provided at the second end of the inner tube. The inner tube may be associated with a heating element and surrounded by three outer tubes 105, 106, 155. The heated transfer line may be translatably received in a housing 107 and may comprise a locking collar 113 rotatably mounted with respect to the housing. A mounting flange 115 may secure the interface to a plinth in use. The inner tube may be mounted with respect to the mounting flange with a floating or movable connection. A gas fitting (200, Fig 12) may be provided wherein the diameter of the central bore of the fitting is less than or equal to the diameter of the bore of the inner tube.

High resolution MS1 based quantification

Mass spectrometer

The objective of the present invention is to improve the robustness, sensitivity, and maintainability of a mass spectrometer to which a liquid chromatograph can be connected. This mass spectrometer is characterized in being provided with: an ion source (100); a mass spectrometry unit; a plurality of flat plates (115) used as electrodes having openings through which ions can be introduced to the mass spectrometer from an orthogonal direction along an ion introduction axis (540); a porous member (140) provided between the mass spectrometry unit and the plurality of flat plates; and a mechanism for feeding gas to the plurality of flat plates on the side opposite from the ion introduction direction; the plurality of flat plates (115) being disposed under atmospheric pressure, and the plurality of electrodes being set at a temperature higher than room temperature.

Staggered chromatography mass spectrometry

An analytical instrument comprises a liquid chromatography system comprising a first column 1, a chromatographic delay line 9 and a splitter 7 arranged and adapted in a mode of operation to split eluent from the first column 1 into a first portion of eluent and a second portion of eluent. The instrument further comprises a first device 5, such as a mass spectrometer. The liquid chromatography system is arranged and adapted in the mode of operation: (i) to pass the first portion of eluent from the splitter 7 to the first device such that a first part of the first portion of eluent arrives at the first device 5 at a first time t1 and a second part of the first portion of eluent arrives at the first device 5 at a second time t2. The system is further arranged and adapted: (ii) to pass the second portion of eluent from the splitter 7 through the chromatographic delay line 9 to the first device 5 such that the passage of the second portion of eluent from the splitter 7 to the first device 5 ...

Staggered chromatography mass spectrometry

Mass-spectrometer interface housing

Mass spectrometer

Probe adaptor assembly

An apparatus (Fig. 6, 200) suitable for connecting an ionisation probe assembly (110) to a mass and/or ion mobility spectrometer comprising an attachment member 122 for releasably attaching, screw fitting 231, a probe assembly (110) to the apparatus (200). A cap 240 for enclosing the attachment member 122 is provided which is configurable to enclose the attachment member 122 when a probe assembly (110) is attached to the apparatus. The cap 240 also has an aperture 241 through which at least a portion of the probe assembly 118 can pass. A device, such as a ball bearing 242, is used to close the aperture 241 when the cap 240 encloses the attachment member 122 and when no probe assembly (110) is attached to the apparatus. This prevents contact with the attachment member 122 when the probe assembly (110) is not attached to the apparatus (200) and the cap 240 is closed.

WITH METABOLIC AGE CONNECTION BIO MARKER AND PROCEDURE FOR THE USE OF IT

HIGHLY SENSITIVE MOLECULAR IDENTIFIKATOR

Biomarker for the diagnosis of pulmonary hypertension (PH)

The present invention relates to a method of diagnosing pulmonary hypertension (PH) in a patient, a method of monitoring the course of pulmonary hypertension in a patient, a method of determining the severity of pulmonary hypertension in a patient, and a method of differentiating between pulmonary hypertension and at least one condition selected from a group consisting of a disease associated with a risk of developing pulmonary hypertension and metabolic syndrome. In addition, the present invention relates to a kit comprising means for carrying out the above methods.

Glucuronylation as acidic post-translational modification on therapeutic monoclonal antibodies

Compositions and methods for identifying glucuronylated protein drug products are provided.

A Kit for Determination of Fentanyl Drugs

The invention discloses a kit for determination of fentanyl drugs, belonging to the field of biotechnology. The specific steps are as follows: the sample is transferred into a centrifuge tube containing acetonitrile in advance for oscillation, extraction and centrifugation; the sample is processed by a purification tube, and the sample solution is in full contact with the mixed purifying agent when it is drawn into the extraction column to complete the purification. After sampling, the plunger is pulled upward continuously, then the filter film is installed at the bottom of the solid phase extraction column and the plunger is pushed downward to make the sample liquid come into contact with the mixed purifying agent again to collect the filtrate. After this, the liquid chromatography-tandem mass spectrometry is employed for analysis. Compared with the traditional purification method, the proposed methodology is simpler, faster, and more efficient. Meanwhile, reducing the number of operation ...

Methods for the diagnosis of dementia and other neurological disorders

Boost devices and methods of using them

A boost device configured to provide additional energy to an atomization source, such as a flame or plasma, is disclosed. In certain examples, a boost device may be used with a flame or plasma to provide additional energy to the flame or plasma to enhance desolvation, atomization, and/or ionization. In other examples, the boost device may be configured to provide additional energy for excitation of species. Instruments and devices including at least one boost device are also disclosed.

Sample introduction interface for analytical processing

Method for detecting muscle degenerative diseases, and method for determining therapeutic efficacy on the diseases

Muscle degenerative diseases can be detected in the early stage and the therapeutic efficacy of a therapeutic agent and/or a therapy method for the diseases can be determined by measuring 11,15-dioxo-9-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (referred to as "Tetranor-PGDM", hereinbelow) in a sample isolated from a subject.

Apparatus for efficient liquid chromatography/mass spectrometry processing

METHODS OF IDENTIFYING AND QUANTIFYING SPHINGOLIPIDS

The present invention relates to a method of identifying and preferably quantifying at least one sphingolipid, in particular the sphingolipid portion in wild-type Cordyceps or Cordyceps derivates. A further aspect relates to a method of identifying wild-type Cordyceps in a Cordyceps sample as well as for identifying Cordyceps derivates in a Cordyceps sample. The methods of the present invention, thus, allow for determining the quality and safety of Cordyceps products and for advantageously differentiating between wild-type Cordyceps and Cordyceps derivates via the ratio and/or presence of certain sphingolipids especially suitable as markers. Wild-type Cordyceps Wild-type Cordyceps Wild-type Cordyceps Cephalosporium Hirsutella sinensis Cordyceps sinensis sinensis _6 -2E5-1 -5 5 15 2S -16 -6 -%24 0 0 6 10 16 PLS . Pts 1 PLS Wild-type Cordyceps Wild-type Cordyceps Mortierella SP Gliocadium roseum *4 4 [ Fig. 6B ...

Truncated Her2 SRM/MRM assay

H:\szp\Interwoven\NRPortbl\DCC\SZP065379_1.docx-14/11/2016 This disclosure provides ten (10) specific peptides, and particular peptide characteristics, from the cell membrane-bound Her2 protein and a diagnostic assay useful for determining the presence and amount of full length and truncated versions of the full-length Her2 protein in cells derived from formalin fixed paraffin embedded tissue.

Treatment of circadian rhythm disorders

Embodiments of the invention relate to the use of a melatonin agonist in the treatment of free running circadian rhythms in patients, including light perception impaired patients, e.g., blind patients, and to methods of measuring circadian rhythm.

Systems and methods for selective quantitation and detection of allergens

The invention relates to methods and systems taking advantage of bioinformatic investigations to identify candidate signature peptides for quantitative multiplex analysis of complex protein samples from plants, plant parts, and/or food products using mass spectroscopy. Provided are use and methods for selecting candidate signature peptides for quantitation using a bioinformatic approach. Also provided are systems comprising a chromatography and mass spectrometry for using selected signature peptides.

Quantitation of tamoxifen and metabolites thereof by mass spectrometry

Provided are methods for determining the amount of tamoxifen and its metabolites in a sample by mass spectrometry. In some aspects, the methods provided herein comprise determining the amount of norendoxifen. In some aspects, the methods provided herein comprise determining the amount of norendoxifen and tamoxifen. In some aspects, the methods provided herein comprise determining the amount of norendoxifen and other tamoxifen metabolites. In some aspects, the methods provided herein comprise determining the amount of tamoxifen, norendoxifen, and other tamoxifen metabolites.

Peptide quantitation assay for differentiating full-length high molecular weight kininogen (HMWK) and cleaved HMWK

Methods for differentiating full-length high molecular weight kininogen (HMWK) and cleaved HMWK in a sample are provided herein. Such methods may comprise treating a biological sample with a protease to generate a plurality of digested peptides, and measuring one or more signature peptides, which are indicative of cleaved HMWK and/or full-length HMWK.

METHOD FOR THE DIAGNOSIS OF NIEMANN-PICK DISEASE

Abstract The present invention is related to a method for diagnosing Niemann-Pick disease in a subject comprising a step a), wherein the step a) comprises detecting a biomarker in a sample from the subject.

Mapping of differential display of proteins

MASS SPECTROMETER

A mass spectrometer and a liquid chromatography system for a mass spectrometer is disclosed. In a peak parking mode of operation solvent from A and B solvent pumps 9,10 is immediately diverted to waste reducing the backpressure on an analytical column 21. Analyte of interest is then allowed to be released from the column 21 at a slower rate by passing fluid from a separate pump 1 through the column 21.

ANALYSIS OF CONJUGATED METABOLITES OF ALCOHOL CONSUMPTION

A method, system, kit and uses for quantifying and normalizing at least one product of ethanol metabolism are provided. A method is provided for quantifying and normalizing at least one product of ethanol metabolism in a sample comprising creatinine. The method comprises adding a predetermined amount of at least one internal standard to the sample; adding deuterated creatinine to the sample; detecting and measuring at least one product of ethanol metabolism, the predetermined amount of at least one internal standard in the sample, the deuterated creatinine, and the creatinine. The method also comprises quantifying the amount of at least one product of ethanol metabolism in the sample using the measurement of the at least one internal standard; quantifying the amount of creatinine in the sample using the measurement of the deuterated creatinine; and normalizing the quantity of the at least one product of metabolism using the measurement of the creatinine.

METHODS AND SYSTEMS FOR PROCESSING SAMPLES ON POROUS SUBSTRATES

Methods and systems for processing samples fixed to a porous substrate generally comprising, a compressor defining one or more fluid isolation areas, a support, for the porous substrate, having an opening corresponding to one or more of the fluid isolation areas of the compressor, an actuator that causes at least a portion of the compressor to press against the porous substrate, a fluid inlet having access to the fluid isolation area at least when the compressor is pressed against the porous substrate, and a fluid outlet to receive fluid, through the opening in the support corresponding to the fluid isolation area of the compressor, at least when the compressor is pressed against the porous substrate.

A SYSTEM AND METHOD FOR HIGH THROUGHPUT SAMPLE PREPARATION AND ANALYSIS USING COLUMN CHROMATOGRAPHY

A system and method high throughput sample preparation and analysis using column chromatography. Each port in a plurality of ports has a port input that interfaces with a first fluid source and a port output. A fluidic circuit is coupled to each port output and to a second fluid source, the fluidic circuit for controlling fluid flow from the plurality of ports and the second fluid source. The fluidic circuit is also coupled to a plurality of chromatography columns. An interface to an analyzer receives output from at least one of the plurality of chromatography columns. The plurality of chromatography columns is moved relative to the analyzer via a translation stage, such that sample output from one of the plurality of chromatography columns can be selectively presented to the analyzer.

A SYSTEM AND METHOD FOR HIGH THROUGHPUT PROCESSING OF DROPLETS

A method for high throughput processing of a plurality of droplets. The droplets are dispensed onto a moving surface (1) and delayed in a delay line (11) in which the droplets hang from the moving surface for at least a specified minimum period of time. A laminate (6) may be spooled onto the moving surface (1) and each droplet may be dispensed onto the laminate (6). At least one operation is performed on each droplet from the group of operations consisting of mixing, diluting, concentration, heating, cooling, humidifying, filtering, and analyzing. The laminate (6) may then, in certain embodiments, be spooled off the moving surface (1), processed, and reused.

A DUAL-COLUMN LC-MS SYSTEM AND METHODS OF USE THEREOF

Methods for achieving complete sequence coverage of monoclonal antibodies by trypsin digestion and dual-column LC-MS system are provided. The disclosed method improves upon current techniques for standard peptide mapping.

GLUCURONYLATION AS A NEW ACIDIC POST-TRANSLATIONAL MODIFICATION ON THERAPEUTIC MONOCLONAL ANTIBODIES

Compositions and methods for identifying glucuronylated protein drug products are provided.

METHODS FOR DETECTING CHROMOGRANIN A BY MASS SPECTROMETRY

Provided are methods for detecting chromogranin A by mass spectrometry. In another aspect, provided herein are methods for quantitating chromogranin A by mass spectrometry. In another aspect, provided herein are methods for prognosis of or measuring the size of neuroendocrine tumors by mass spectrometry.

PEPTIDE QUANTITATION ASSAY FOR DIFFERENTIATING FULL-LENGTH HIGH MOLECULAR WEIGHT KININOGEN (HMWK) AND CLEAVED HMWK

Methods for differentiating full-length high molecular weight kininogen (HMWK) and cleaved HMWK in a sample are provided herein. Such methods may comprise treating a biological sample with a protease to generate a plurality of digested peptides, and measuring one or more signature peptides, which are indicative of cleaved HMWK and/or full-length HMWK.

PSEUDO INTERNAL STANDARD METHOD, DEVICE AND APPLICATION FOR MASS SPECTROMETRY QUANTITATIVE ANALYSIS

A simulated internal standard method, device and application for mass spectrometry quantitative analysis. The method comprises steps: taking a standard, and formulating same into standard solutions with different concentrations by using a blank substrate of a sample to be tested, and then taking the same standard, and formulating same into internal standard solutions with one to several concentrations by using the blank substrate of the sample to be tested; processing the standard solutions and the internal standard solutions with different concentrations, through a sample processing step, into a standard sample and an internal standard sample; successively injecting the standard sample and the internal standard sample into a chromatography-mass spectrometry system to be analysed and measured; plotting a ratio of peak areas of the standard sample and the internal standard sample against the concentrations to obtain a calibration curve of simulated internal standard method quantification ...

METHODS FOR IMPROVING CARDIOVASCULAR DISEASE MANAGEMENT

METHOD FOR CALIBRATING DETECTED MASS IN MASS SPECTROMETRY SYSTEM

With respect to a mass spectrograph designed to feed a solution to interface (20) between separation analysis equipment (10) and mass spectrometer (50), any detected mass is calibrated by mixing an internal standard substance for mass calibration in the solution (sheath liquid for obtaining an electrical contact between migration buffer (16) of capillary electrophoresis unit (10) or mobile phase of liquid chromatograph or separation analysis equipment and a mass spectrometer). Consequently, without the need of spray for calibration and without the use of post-column introduction method, a mass calibration o f measured substance can be simply and easily.

LIPID SCREENING PLATFORM ALLOWING A COMPLETE SOLUTION FOR LIPIDOMICS RESEARCH

Known lipid molecules of a matrix are grouped into lipid classes and the lipid classes are further grouped into a pass-through group and a mobility separation group based on isobaric interferences. A separation system separates known lipid molecules from a matrix sample and an ion source ionizes the matrix sample. Two injections are performed. For the first injection a DMS device is put into passive mode, and for the second injection the DMS device is used to resolve isobaric interferences. A tandem mass spectrometer performs MRM scans of the pass-through group for the first injection and MRM scans of the mobility separation group for the second injection. A processor quantitates each lipid molecule in the matrix sample by comparing the MRM intensity values obtained for the first and second injections to MRM intensity and concentration values for known standards of the known lipid molecules of the matrix.

A METHOD FOR THE RELATIVE QUANTIFICATION OF CHEMICAL COMPOUNDS CONTAINED IN A MIXTURE OF DIFFERENT BIOLOGICAL SAMPLES

The present invention relates to a method for the simultaneous identification of one or more chemical compounds contained in a sample, from an analytical measurement of a pool of two or more of the said samples, wherein a measured intensity of a first and second signal is representative for an abundance of respectively the first and second chemical compound in the first sample, and a measured intensity of a third and fourth second signal is representative for an abundance of respectively a third and fourth chemical compound in the second sample, wherein respectively the first and third, and the second and fourth compound may be the same or different, wherein the signal intensities are organized in a matrix aij of m columns and n rows, wherein n is = 2 and corresponds to the number of chemical compounds in the pool, wherein m = 2 and corresponds to the number of samples in the pool, wherein aij corresponds to a signal intensity measured for compound i present in sample j, (1) wherein: (2 ...

Method and apparatus for sample inclusion in HPLC columns and converting the samples in a MS/LC MS analysis system for determining and quantification of analytes, such as this is necessary for the determination of drug typically mirrors or biomarkers.

Die Erfindung betrifft eine HPLC-Säule (15) mit einem Probenaufnahmeteil als eigentlicher Probenträger, welcher einzeln oder mehrfach in einer individuell markierten Kassette (11) integriert ist, die Probenaufnahme, den Probentransport, die Probenzwischenlagerung und Integration in das LC-MS-System (36) mit der Kassette (11) zusammen erfolgt, ein druckkontrolliertes Klammersystem den Probenträger mit der getrockneten Probe aufnimmt und die Methode zur analytischen Aufgabe und Zuordnung der Resultate via die Markierung auf der Kassette erfolgt.

DVUKhKOLONOChNAYa JX - MS SYSTEM AND METHODS FOR ITS USE

Mass spectrometer

METHOD OF GENERATING AN INCLUSION LIST FOR TARGETED MASS SPECTROMETRIC ANALYSIS

A method for determining the Gardenia yellow product hide flowers acid derivatives in the total amount and composition of the method

METHOD FOR QUANTIFYING OR DETECTING PIVKA-II BASED ON MULTIPLE SIMULTANEOUS QUANTITATION

Disclosed in the present invention are a method for accurately quantifying DCP used as a marker for liver cancer using MRM technology based on liquid chromatography mass spectrometry, and a method for monitoring the early diagnosis and treatment prognosis of liver cancer using the same. The method according to the present invention can diagnose liver cancer rapidly, economically, and accurately compared to conventional immunoassay. COPYRIGHT KIPO 2017 ...

Method for analyzing Vitis vinifera extract

Analysis method for aldehyde compounds in metal plating solutions

métodos para o diagnóstico da doença de niemann-pick, método para determinação do curso da doença de niemann-pick, método para determinação da eficácia de pelo menos um tratamento, uso de análise espectrométrica de massa e kit

diagnostic method based on patterns and/or [...][...] for support vectors applied to mass spec

Methods for the structure and purity determination of serotonin transporter SPECT imaging agent ADAM and its precursor, SnADAM

The present invention provides high pressure liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the structure determination of serotonin transporter SPECT imaging agent [123I]ADAM and its precursor, SnADAM. The present invention also provides a high performance liquid chromatography for the determination of purity of SnADAM.

CAPILLARY COLUMN WITH FRITTED TIP

The present invention is directed to a capillary tube having an emitter tip with a polymerized porous frit therein and to methods of making such a capillary tube.

SEPARATION CARTRIDGES AND METHODS FOR FABRICATION AND USE THEREOF

Embodiments of the invention provide separation cartridges, methods for fabricating separation cartridges, and methods for using separation cartridges. One aspect of the invention provides a separation cartridge including a first end, a second end, and one or more sorbents located between the first end and the second ends, the one or more sorbents arranged from the first end to the second end in order of increasing hydrophobicity. Another aspect of the invention provides a method of creating a separation cartridge having varying hydrophobicity. The method includes loading a filtration material and a cross-linking agent into a cylinder and selectively exposing the material to an energy source to selectively initiate a cross-linking reaction within the filtration material.

BIOMARKERS FOR MONITORING TREATMENT OF NEUROPSYCHIATRIC DISEASES

Methods for identifying and measuring pharmacodynamic biomarkers of neuropsychiatric disease, and for monitoring a subject's response to treatment.

URINE BASED DETECTION OF A DISEASE STATE CAUSED BY A PNEUMOCOCCAL INFECTION

There is provided a method of diagnosing a disease state in a subject. The disease state is caused or effected by pneumococcal infection. The method includes obtaining a biological test sample from the subject. The biological sample includes at least one metabolite selected from the group consisting of citrate, trigonelline, acetylcarnitine, acetone, myo-inositol, 3-hydroxybutyrate, glucose and carnitine. A respective concentration of each one of the at least one metabolite is compared with a predetermined concentration value associated with a corresponding one of the at least one metabolite. The predetermined concentration value is indicative of the disease state. For example, the biological sample includes any one of citrate, trigonelline, acetylcamitine, acetone, myoinositol, 3-hydroxybutyrate, glucose and carnitine. As a further example, the biological samples include any combination of citrate, trigonelline, acetylcamitme, acetone, myo-xnositol, 3- hydroxybutyrate, glucose and carnitine ...

HIGH THROUGHPUT AUTOSAMPLER

A system for high throughput sample preparation and analysis. The system includes a chromatography column including an insoluble matrix. A fluidic circuit is capable of passing a fluid over the insoluble matrix in a first direction such that an analyte in the fluid binds to the insoluble matrix, and back-eluting an elution fluid over the insoluble matrix in a second direction opposite the first direction to output a sample that includes the analyte. A controller controls the fluidic circuit to periodically perform the steps of passing the fluid over the insoluble matrix and back-eluting the elution fluid over the insoluble matrix to output a plurality of samples at a periodic rate.

PROCESS FOR ESTABLISHING DIRECT DIAGNOSTIC EVIDENCE OF PATHOGENIC, GENETICALLY-CONDITIONED POINT MUTATIONS

The invention relates to a rapid process for medical and diagnostic, qualitative and quantitative protein analysis of the exchange of individual amino acids with pathogenic or non-pathogenic effects on the organism. The medical and diagnostic analysis is achieved by combination of enzymatic or chemical separation of the isolated peptide, chromatographic separation of the fragments and analysis by mass spectrometry, and of direct liquid chromatography-mass spectrometry (LC/MS) and indirect matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS), and analysis by capillary electrophoresis. By comparing the protein samples of healthy people with the samples of sick people, said process can be used to determine novel, presently unknown mutations, and to quantify the expression and incorporation of a wild type to form a mutant.

HIGH THROUGHPUT SIZE-EXCLUSIVE METHOD OF SCREENING COMPLEX BIOLOGICAL MATERIALS FOR AFFINITY LIGANDS

La présente invention concerne un procédé amélioré, rapide et à exclusion de taille et permettant une recherche systématique de ligands, dans des matériaux biologiques complexes, notamment dans des échantillothèques, dans des produits naturels ou des échantillons, ou des mélanges de composés purs. Les ligands considérés sont des ligands de faible masse moléculaire se liant spécifiquement à une protéine cible. La recherche se fait par séparation à exclusion de taille, ultrafiltration et spectrométrie de masse.

METHODS FOR SEPARATION AND DETECTION OF KETOSTEROIDS AND OTHER CARBONYL-CONTAINING COMPOUNDS

Methods for enhancing detection by mass spectroscopy (MS) and/or chromatographic separability of carbonyl-containing compounds such as steroids are disclosed. Reaction of a carbonyl compound with a sulfonhydrazide compound provides a sulfonhydrazone with enhanced ionization efficiency during the electrospray ionization process. In a particularly disclosed embodiment, derivatization of catechol estrogens with p-toluenesulfonhydrazide enhances both detection by atmospheric pressure ionization-MS (API-MS), such as electron spray ionization-MS (ESI-MS) and separation by liquid chromatography (such as HPLC) under reverse phase conditions. In yet other embodiments, the sulfonhydrazone is further reacted with a sulfonyl halide under alkaline conditions to derivatize hydroxyl groups in the compound. Prior formation of the sulfonhydrazide derivative protects the carbonyl bond of the compound during subsequent alkaline reaction with the sulfonyl halide.

MULTI COLUMN CHROMATOGRAPHY SYSTEM

The present invention relates to a method and apparatus for chromatographically analyzing each of a plurality of samples in detector, comprising an autosampler to contain a plurality of samples for chromatographic analysis and a plurality of chromatographic systems, each system comprising one or more pumps and one or more chromatography columns. A detector is included for detecting compounds in the samples from each of the chromatography systems along with a valve positioned between the detector and the plurality of chromatography systems, the valve permitting each sample to reach the detector in sequence. A computer control device is included which adjusts the introduction of samples from the autosampler into the plurality of chromatography systems as well as the position of the valve to sequentially separate and deliver compounds within the samples to the detector.

HIGH THROUGHPUT ANTIBODY VARIANT SCREENING METHOD

Disclosed is a high throughput method for selecting an antibody variant amino acid sequence of interest from a plurality of antibody variant amino acid sequences. The method is particularly useful in the engineering of improved antibodies.

Porous cyclodextrin polymeric materials and methods of making and using same

A nucleophilic substitution reaction to crosslink cyclodextrin (CD) polymer with rigid aromatic groups, providing a high surface area, mesoporous CD-containing polymers (P-CDPs). The P-CDPs can be used for removing organic contaminants from water. By encapsulating pollutants to form well-defined host-guest complexes with complementary selectivities to activated carbon (AC) sorbents. The P-CDPs can rapidly sequester pharmaceuticals, pesticides, and other organic micropollutants, achieving equilibrium binding capacity in seconds with adsorption rate constants 15-200 times greater than ACs and nonporous CD sorbents. The CD polymer can be regenerated several times, through a room temperature washing procedure, with no loss in performance.

Analyzing-device controller

A specimen information storage section (361) holds specimen information showing the relationship between a number of specimens to be analyzed and compounds whose quantities need to be determined. An analysis method storage section (362) holds the files of analysis methods created by an administrator. When an operator selects and indicates analysis methods to be used in an analysis, a method information creation processor (32) extracts compound information from the selected analysis methods and creates method information showing the correspondence between the analysis methods and the compounds to be analyzed. When the operator registers the specimen numbers of the analysis targets, a used-method automatic determiner (34) refers to the specimen information and method information to identify a suitable analysis method for each compound in the registered specimens. An analysis schedule creator (35) creates a schedule table in which the specimens and analysis methods are described in order of ...

HIGH-PRESSURE TUBING

A method for making conduits includes inserting an inner tube into an outer tube and melting a portion of the inner tube to form a bond with the outer tube. The inner tube includes a polymeric material and the outer tube includes a material having a greater yield strength than the polymeric material. A conduit includes one or more inner tubes at least one of which is melt-bonded to one or more outer tubes. An analytical instrument includes a separation column, a solvent reservoir and pump, a sample injector, a detector to observe an eluent of the separation column, and tubing to transport fluid between components of the instrument.

Ionizable isotopic labeling reagents for relative quantification by mass spectrometry

Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications ...

Tandem Mass Tag Multiplexed Quantitation of Post-Translational Modifications of Proteins

Disclosed are methods of quantifying multiple quality attributes, such as post translational modifications, of multiple samples in a single mass spectrometry (MS) run, including contacting two or more samples with a digesting solution under conditions sufficient to digest samples, wherein each sample is digested separately and the digesting solution is a Tris-free buffer solution; contacting each of the two or more digested samples with a specific Tandem Mass Tag (TMT) labeling reagent under conditions sufficient to label peptides within each of the digested samples with the specific TMT labeling reagent; quenching labeling of peptides within each of the two or more digested samples; combining equal volumes of the two or more labeled, digested samples into a single combined sample solution; and analyzing the single combined sample solution by targeted mass spectral analysis, thereby allowing multiple quality attributes of the two or more samples to be quantified in a single mass spectrometry ...

Sample introduction interface for analytical processing

An interface for introducing a non-gaseous sample as a predetermined gaseous form into an accelerator mass spectrometer which comprises a nebulizer that receives the non-gaseous sample to provide a fine spray of the sample, a converter that receives at least a portion of said fine spray and converts the desired elements to the predetermined gaseous form and a flow line that transports the predetermined gaseous form to the accelerator mass spectrometer.

Capillary column chromatography process and system

A microfluidic system is provided for separating components of many fluid samples in a parallel fashion through an array of capillary conduits. The system includes capillary conduits for receiving fluid samples, and for effecting separation of substituents of the sample by passing the sample through a corresponding array of capillary separation conduits containing a solid separation medium. The microfluidic circuit is made of three or more substrate layers and preferably includes etched channels in different layers that are dimensioned relative to one another to provide for retaining the solid composition within the capillary separation conduits. The system also includes an array of detector flow cells in fluid communication with the capillary separation conduits, and an array of high pressure connectors for connecting discrete capillary tubes to the fluid passages in the microfluidic circuit for introducing and removing the fluid samples from the system. The connections for the capillary ...

Systems and methods for mass calibration

A method includes producing ions from one or more calibrant species and delivering the ions to a mass analyzer, and measuring a first set of mass related physical values for the ions from the one or more calibrant species. The method further includes producing ions from a sample and delivering the ions to a mass analyzer, and measuring a second mass related physical value for a first sample ion species. The first sample ion species has a mass-to-charge ratio outside of the range of the mass-to-charge ratios of the calibrant ion species. Additionally, the method includes calculating a calibration curve based on the first set of mass related physical values and second mass related physical value, and modifying at least one instrument parameter based on the calibration curve.

CONTINUOUS FLOW MOBILITY CLASSIFIER INTERFACE WITH MASS SPECTROMETER

A continuous flow mobility classifier provide the ability to perform two-dimensional separation in mass spectrometry. An ionization system is used to ionize a sample. A differential mobility analyzer (DMA) (e.g., a nano-radial DMA) is coupled to the ionization system and to a mass spectrometer. The nano-RDMA is configured to separate the ionized sample by mobility for subsequent mass analysis by the mass spectrometer.

LC-MFR-MS-Based Method and Apparatus for Screening a New Drug Candidate

The present invention relates to a method for screening a new drug candidate using a liquid chromatography/microfluidic device/mass spectrometry system, and to a liquid chromatography/microfluidic device/mass spectrometry system. The present invention involves the detection of an interaction between molecules on a real-time basis through adjustment of a microreaction between traces of natural material or synthesized new drug candidates and a target material (protein or cell, etc.), thus developing materials for new drug candidates at a lower cost and with high efficiency, while improving quality of life and reducing medical costs. The present invention can be valuably used in increasing new scientific technology through the convergence of nanotechnology, biotechnology, and analytical chemistry technology.

IDENTIFICATION AND QUANTIFICATION OF CONJUGATED PEPTIDES IN ANTIBODY DRUG CONJUGATES BY MASS SPECTROMETRY

The present disclosure relates to a streamlined, complete workflow for the qualitative and the quantitative analysis of conjugated peptides from antibody-drug conjugate (ADC) compounds.

System and method for grouping precursor and fragment ions using selected ion chromatograms

LC/MS data generated by an LC/MS system is analyzed to determine groupings of ions associated with originating molecules. Ions are grouped initially according to retention time, for example, using retention time or chromatographic peaks in mass chromatograms. After initial groupings are determined based on retention time, ion peak shapes are compared to determine whether ions should be excluded. Ions having peak shapes not matching other ions, or alternatively a reference peak shape, are excluded from the group.

Mass spectrometric determination of non-derivatized, non-metabolized vitamin D

The invention relates to the detection of non-metabolized vitamin D. In a particular aspect, the invention relates to methods for detecting underivatized non-metabolized vitamin D by mass spectrometry.

BIOMARKERS FOR MONITORING TREATMENT OF NEUROPSYCHIATRIC DISEASES

Methods for identifying and measuring pharmacodynamic biomarkers of neuropsychiatric disease, and for monitoring a subject's response to treatment.

Microfluidic devices for liquid chromatography and mass spectrometry

In one aspect, a microfluidic device includes a substrate with a top surface and a raised channel architecture in which at least one channel is formed and defined across a top surface of the substrate and between raised side walls such that a floor of the channel is coplanar with the top surface. The device has a cover positioned over the substrate in alignment with the substrate and including a seal portion that is sealingly received between the raised side walls so as to seal the at least one channel. In addition, the device includes a column packing material disposed within the at least one channel between the raised side walls prior to sealing the at least one channel by merely only inserting the seal portion of the cover within the at least one channel between the raised side walls.

Methods of liquid chromatography for anionic compounds

The present disclosure generally relates to improved methods for separating and analyzing compounds by liquid chromatography, particularly when coupled with mass spectrometry. The methods include the addition of an additive to a mobile phase carrying a sample. The mobile phase additive may be effective for improving peak shapes of targeted analytes in acquired data, and/or eliminating or at least reducing ion suppression. The methods are particularly suited for anionic compounds such as phosphorylated compounds.

DUAL-COLUMN LC-MS SYSTEM AND METHODS OF USE THEREOF

Methods for achieving complete sequence coverage of monoclonal antibodies by trypsin digestion and dual-column LC-MS system are provided. The disclosed method improves upon current techniques for standard peptide mapping.

APPARATUS FOR AUTO-PRETREATING SUGAR CHAIN

To provide an autoanalyzer for analyzing a sugar chain contained in a biological sample, in particular, serum. Namely, it is intended to provide a method of analyzing a sugar chain in a sample, which comprises the following steps: A) the sugar chain-releasing step of releasing the sugar chain in the sample; B) the detection sample-preparing step of preparing the released sugar chain for detection; and, in the case of conducting mass spectrometry using a plate, C) the step of forming a plate for the mass spectrometry having the captured sugar chain dotted thereon which comprises the step of providing the tagged sugar chain sample solution obtained in the step B) on a collection plate; and, if required, the step of conducting an operation in a solid phase support-enclosed plate to form the plate for mass spectrometry; and D) the step of analyzing the sugar chain to be assayed.

Improved chromatography resin, and methods and devices related thereto.

The invention relates to the field of analytical and preparative chemistry. Among others, it relates to an improved chromatographic resin and to means and methods involving use of the resin for the (on-line) clean up of complex test samples, such as biological samples. Provided is a chromatographic resin comprising a rigid polymer that is functionalized with at least one ligand capable of binding to a molecule of interest, wherein said ligand is covalently attached to the polymer via a small hydrophilic moiety based on a compound having 1-10 C-atoms and comprising a multiplicity of hydrophilic groups.

Preparative liquid chromatograph using plural detectors

Miniaturized device for sample processing and mass spectroscopic detection of liquid phase samples

A miniaturized planar device is described for use in a liquid phase analysis system. The device comprises a separation compartment that is in fluidic communication with a make-up flow channel and a channel compartment that terminates in a on-device mass spectrometer delivery means. The device is formed by microfabrication of microstructures in novel support substrates. The invention herein is used for the analysis of small and/or macromolecular and/or other solutes in the liquid phase.

質量分析における安定同位体標識標的ペプチド断片の作製方法

肝実質細胞中のＰ４５０タンパク質のアイソフォームの質量分析による定量

ЛЕЧЕНИЕ НАРУШЕНИЙ ЦИРКАДНОГО РИТМА

Изобретение относится к области медицины и представляет собой способ подгонки циркадного ритма кортизола к 24-часовому циркадному ритму и сохранения 24-часового циркадного ритма. Способ включает пероральное введение пациенту эффективного количества тазимелтеона один раз в день перед отходом ко сну, предпочтительно за 0,5-1,5 ч до требуемого времени засыпания, предпочтительно доза тазимелтеона составляет 10-00 мг. Пациенты могут иметь нарушенное восприятие света или являться слепыми. Введение тазимелтеона могут начинать в день, когда акрофаза aMT6s в моче будет иметь место в период от 5,5 ч до требуемого времени пробуждения и до 2,5 ч после требуемого времени пробуждения. Осуществление изобретения обеспечивает нормализацию циркадного ритма кортизола. 7 з.п. ф-лы, 17 ил., 7 табл.

Acquisition and Analysis of Mixed Ion Populations in a Mass Spectrometer

A method of obtaining and analyzing a mass spectrum of a sample comprising components is characterized by: setting values of a first energy level and a second energy level; chromatographically separating the components; ionizing a portion of the separated components to create precursor ions; introducing a first portion of the precursor ions into a collision or reaction cell and generating a first sub-population of ions corresponding to the first energy level; introducing a second portion of the precursor ions into the cell and generating a second sub-population of ions corresponding to the second energy level; transferring a mixture of the first and second sub-populations of ions into a mass analyzer; producing an analysis of the ions of the mixture; varying the value of at least one of the first and the second energy levels according to a pre-determined cyclical variation; repeating various above steps; and analyzing the time-variation of the analyses.

Techniques for mass spectrometry peak list computation using parallel processing

Described are techniques for processing data. Sample analysis is performed generating scans of data. Each scan comprises a set of data elements each associating an ion intensity count with a plurality of dimensions including a retention time dimension and a mass to charge ratio dimension. The scans are analyzed to identify one or more ion peaks. Analyzing includes filtering a first plurality of the scans producing a first plurality of filtered output scans. The filtering including first filtering producing a first filtering output, wherein the first filtering includes executing a plurality of threads in parallel which apply a first filter to the first plurality of scans to produce the first filtering output. Each of the plurality of threads computes at least one filtered output point for at least one corresponding input point included in the plurality of scans. Analyzing includes detecting one or more peaks using the filtered output scans.

Methods and systems for in vivo clinical data measurement of analytes

The present invention provides apparatuses, systems, and methods for real-time measuring of analytes in a biological fluid sample of a subject. In particular, the present invention provides a combination of micro-dialysis catheter, a micro-volume pump, and a spectrometer device that are operatively connected to one another to provide real-time measurement of analytes in a biological fluid sample of a subject.

Methods and Apparatus for Identifying Mass Spectral Isotope Patterns

A method for automatically identifying groups of related peaks generated in a chromatography-mass spectrometry experiment comprises automatically choosing a time window defining a region of interest for mass spectral data generated by the experiment; automatically constructing a plurality of extracted ion chromatograms (XICs) for mass spectral peaks observed within the region of interest; automatically detecting and characterizing chromatogram peaks within each XIC and automatically generating synthetic analytical fit peaks thereof; automatically discarding a subset of the synthetic analytical peaks which do not satisfy noise reduction rules; automatically performing a respective cross-correlation score calculation between each pair of synthetic analytical fit peaks; and automatically identifying groups of correlated peaks in at least one mass spectrum within the region of interest.

Quantification of impurities for release testing of peptide products

The present invention relates to a method for the quantitative determination of an impurity present in a peptide product, wherein the impurity cannot be separated from other impurities or the main product. The method particularly involves the use of high resolution mass spectrometry (MS) detection with or without high performance liquid chromatography (HPLC). The method can be used for the investigation of the quality of peptides and proteins, particularly of pharmaceutical peptides and proteins.

SYSTEM AND METHOD FOR GROUPING PRECURSOR AND FRAGMENT IONS USING SELECTED ION CHROMATOGRAMS

LC/MS data generated by an LC/MS system is analyzed to determine groupings of ions associated with originating molecules. Ions are grouped initially according to retention time, for example, using retention time or chromatographic peaks in mass chromatograms. After initial groupings are determined based on retention time, ion peak shapes are compared to determine whether ions should be excluded. Ions having peak shapes not matching other ions, or alternatively a reference peak shape, are excluded from the group. 120-. (canceled)21. A method of grouping ions comprising:performing an experiment using a sample mixture including performing a chromatographic separation and mass spectral analysis of the sample mixture;detecting ions using data obtained from the experiment, wherein each of the ions is characterized by characteristics including a retention time and a chromatographic peak shape;selecting a reference retention time;determining a group of one or more of the ions based on the reference retention time; andexcluding from the group any ion having a chromatographic peak shape that is not similar to a reference chromatographic peak shape.22. The method of claim 21 , wherein the reference retention time and reference chromatographic peak shape characterize a reference ion.23. The method of claim 22 , further comprising:determining a portion of the ions of interest;selecting the reference ion from the portion of the ions of interest, wherein the reference ion has a maximum intensity of the portion.24. The method of claim 22 , wherein each ion in the group is determined in accordance with a set of one or more rules including one or more rules indicating that each ion in the group has a common retention time and similar peak shape with respect to other ions in the group.25. The method of claim 24 , wherein the set of one or more rules includes at least one rule specifying that an ion is included in the group only if the ion is has a mass that is lower than a mass of the ...

LC-MS CONFIGURATION FOR PURIFICATION AND DETECTION OF ANALYTES HAVING A BROAD RANGE OF HYDROPHOBICITES

Systems, apparatuses, kits, and methods for purification and analysis of analytes having a broad range of hydrophobicities by liquid chromatography-mass spectrometry (LC-MS). Using one set of liquid chromatography columns, one set of mobile phase buffers, and, optionally, a single ionization method (e.g., electrospray ionization), a wide range of analytes can be purified and analyzed on a liquid chromatography-mass spectrometry (LC-MS) system. LC-MS purification and analysis of analytes having a broad range of partition coefficients is accomplished by selecting LC run parameters and MS system parameters that are particular to different classes of analytes without having to make column or buffer changes or any other hardware configuration changes to the LC-MS system. The methods, systems, and kits described herein provide for substantially increased speed/throughput and ease of use for a wide range analytes with essentially no compromise in specificity for individual analytes relative to previously described methods. 1. A method , comprising:providing two or more analytes selected from a first group and a second group, wherein the log partition coefficients (logP) of the two or more analytes selected from the first group and the second group are separated by at least about 4.5 logP units;purifying at least one analyte from each of the first and second groups using a single analytical liquid chromatography column of a liquid chromatography system, one aqueous mobile phase buffer solution of the liquid chromatography system, and one substantially non-aqueous mobile phase buffer solution of the liquid chromatography system; andanalyzing the analytes from the first and second groups using a mass spectrometer.2. The method of claim 1 , wherein the two or more analytes are contained in different samples.3. The method of claim 1 , wherein the two or more analytes are contained in a single sample.4. The method of claim 1 , wherein the two or more analytes are purified and ...

Vitamin d metabolite determination utilizing mass spectrometry following derivatization

The invention relates to the detection of vitamin D metabolites. In a particular aspect, the invention relates to methods for detecting derivatized vitamin D metabolites by mass spectrometry.

METHODS OF ADMINISTERING TETRAHYDROBIOPTERIN, ASSOCIATED COMPOSITIONS, AND METHODS OF MEASURING

The present invention is directed to treatment methods of administering tetrahydrobiopterin, including in oral dosage forms, in intravenous formulations, and with food. Also disclosed herein are biopterin assays for measuring the amount of biopterin and metabolites of biopterin in a sample. 1. A method of orally administering tetrahydrobiopterin (BH4) , comprising administering to a human in need thereof a therapeutically effective amount of BH4 or a pharmaceutically acceptable salt thereof , and informing said human that absorption of said BH4 or pharmaceutically acceptable salt thereof is increased when it is ingested with food compared to when ingested without food.212.-. (canceled)13. A method of increasing gut retention time of tetrahydrobiopterin (BH4) or a pharmaceutically acceptable salt thereof in a subject comprising administering a formulation to said subject , said formulation comprising (1) BH4 or pharmaceutically acceptable salt thereof and (2) an agent that slows gut motility ,wherein the BH4 or pharmaceutically acceptable salt thereof administered via the formulation has a longer gut retention time in comparison with a control formulation of BH4 or pharmaceutically acceptable salt thereof not having an agent that slows gut motility.1419.-. (canceled)20. An oral formulation of tetrahydrobiopterin (BH4) or a pharmaceutically acceptable salt thereof , comprising BH4 or pharmaceutically acceptable salt thereof and an agent that slows gut motility.2125.-. (canceled)26. A liquid formulation of tetrahydrobiopterin (BH4) or a pharmaceutically acceptable salt thereof , comprising an aqueous solution of BH4 or pharmaceutically acceptable salt thereof , an antioxidant , and a pH buffer.27. A dry powder formulation of tetrahydrobiopterin (BH4) or a pharmaceutically acceptable salt thereof for constitution into an aqueous solution , comprising a dry powder mixture of BH4 or pharmaceutically acceptable salt thereof , an antioxidant , and a pH buffer.2837.-. ( ...

IN-VIAL MICROEXTRACTION (IVME) SYSTEMS AND THEIR METHOD OF MAKING

An in-vial microextraction (IVME) device is a vial with at least a portion of the inner surface having a sol-gel coating that absorbs at least one target analyte. The sol-gel coating is a metal oxide comprising coating that is formed from a tri-and/or tetra-functional metal comprising precursor that condenses to form a gel network. The IVME device can be used to prepare a sample by the contacting of the IVME device with a solution or suspension. An analytical method is enabled where the absorbed analyte from the IVME device is subsequently desorbed with a solvent or solution or thermally desorbed and analyzed using GC-MS or LC-MS or other analytical instrument for separation and detection. 1. An in-vial microextraction (IVME) device; comprising , a vial with at least a portion of the inner surface having a sol-gel coating that absorbs at least one target analyte.2. The IVME device according to claim 1 , wherein the vial is glass claim 1 , plastic claim 1 , ceramic claim 1 , or metal.3. The IVME device according to claim 1 , wherein the sol-gel coating comprises a metal oxide comprising gel from a precursor of the structure: RRRRM claim 1 , wherein: Ris optional;{'sup': 1', '2', '3', '4', '1', '2', '3', '4', '1', '2', '3', '4, 'M is silicon, titanium, aluminum, zirconium, germanium, barium, gallium, indium, thallium, vanadium, cobalt, nickel, chromium, copper, iron, lanthanum, niobium, zinc, or boron; at least two of R, R, R, and Rare independently alkoxy, hydroxy, halides, hydrogen or dialkylamino, and remaining R, R, R, and Rare independently substituted or unsubstituted alkyl, aryl, cyanoalkyl, fluoroalkyl, phenyl, cyanophenyl, biphenyl, cyanobiphenyl, dicyanobiphenyl, cyclodextrin moieties, crown ether moieties, cryptand moieties, calixarene moieties, dendrimer moieties, graphene moieties, carbon nanotubes, or wherein the R, R, R, and Ris chiral or achiral.'}4. The IVME device according to claim 3 , wherein the metal oxide comprising gel further comprises a ...

Methods Of Detecting Cancer

The present disclosure is directed toward methods and kits for detecting cancer, and in particular breast cancer, in a subject by measuring the levels of at least one of the identified markers, as compared to a control. The expression of the markers in Table 2A is increased in samples from subjects with cancer as compared to the expression level in subjects without cancer and the expression of the markers in Table 2B are decreased in samples from subjects with cancer as compared to the expression level in subjects without cancer. The sample may be lacrimal secretions or eye wash fluid, saliva, or other biological fluids. The kits may include an eye wash kit, collection tubes and protease inhibitors, or protein stabilizers.

Method and System for Monitoring Biomolecule Separations by Mass Spectrometry

Monitoring biomolecule separations by mass spectrometry is described. The mixture to be separated is introduced into a first fluidic stream, which then passes through a chromatography column. Small samples are periodically taken from the first fluidic stream as it leaves the chromatography column and injected into a first branch of a second fluidic stream. Low molecular weight components detrimental to the efficient operation of the mass spectrometer are removed by an in-line dialysis cell. A second fraction of the second fluidic stream acts as the dialysate. In a second and preferred system provided in accordance with the present teaching, the first fraction of the second fluidic stream is further split downstream of the sampling mechanism through the use of a three-way connector. Approximately 0.3 to 5 microliters per minute continues through the dialysis cell and thereafter to the electrospray emitter of the mass spectrometer. 1. A system for effecting biomolecule separations and monitoring said separations by mass spectrometry , the system comprising:a liquid chromatography module configured to effect at least a partial separation of biomolecule components dissolved in a liquid, the dissolved biomolecule components being carried through the liquid chromatography module in a first fluidic stream;a sampling module in fluid communication with and provided downstream of the liquid chromatography module, the sampling module being configured to periodically transfer an aliquot of the liquid in the first fluidic stream into a second fluidic stream;a dialysis module in fluid communication with and provided downstream of the sampling module, the dialysis module being configured to dialyse the liquid in the second fluidic stream; anda mass spectrometer in fluid communication with and provided downstream of the dialysis module, the mass spectrometer being configured to detect components in the dialysed liquid in the second fluidic stream;wherein operably, the first fluidic ...

CHROMATOGRAPH DEVICE

A chromatograph device which makes it possible to suppress a carry-over phenomenon. A sample injection unit for collecting a liquid sample and injecting a predetermined amount of liquid sample into a mobile phase; a sample introduction tube a distal end section of which has a needle formed therein and a terminal end section of which is connected to the sample injection unit; a separation column which is coupled via a column coupling tube to the sample injection unit, and through which the mobile phase where the liquid sample has been injected passes; and a detection unit that is connected to the separation column and detects a component in the liquid sample. The column coupling tube is provided with an ultrasonic vibrator for vibrating the tube. 15-. (canceled)6. A chromatograph device comprising:a sample injector collecting a liquid sample and injecting a predetermined amount of liquid sample into a mobile phase;a sample introduction tube a distal end section of which has a needle formed therein and a terminal end section of which is connected to the sample injector;a separation column which is coupled via a column coupling tube to the sample injector, and through which the mobile phase where the liquid sample has been injected passes;a detector connected to the separation column and detecting a component in the liquid sample; anda cleaning mechanism including a container in which water is accommodated and the column coupling tube is immersed in the water and an ultrasonic vibrator attached to the container and removing a residual component in the column coupling tube by the ultrasonic vibrator vibrating the column coupling tube by generating ultrasonic waves.7. The chromatograph device according to claim 6 , comprising:a needle driver moving the needle; anda table where a plurality of sample containers accommodating liquid samples are placed.8. The chromatograph device according to claim 7 , comprising a controller operating the ultrasonic vibrator between liquid ...

HEAVY PEPTIDE APPROACH TO ACCURATELY MEASURE UNPROCESSED C-TERMINAL LYSINE IN ANTIBODIES

The present disclosure provides a method for measuring post-translational modifications in proteins such as antibodies. In particular, the method may be used to quantify C-terminal truncation in antibodies that incorporates heavy isotopic standards for both the unprocessed C-terminal K peptide and the truncated C-terminal K peptide to build a calibration curve and quantify this PTM using mass spectrometry. Quantification of post-translational modifications may occur in a single liquid chromatography tandem mass spectrometry (LC-MS) run. 1. A method for quantifying unprocessed C-terminal lysine in a peptide (K peptide) , comprising:mixing a set of heavy C-terminal peptide standards with a peptide digest;generating a calibration curve of a peptide signal of the unprocessed C-terminal K response relative to that of a truncated (des-K) peptide; andanalyzing and quantifying the percentage of K peptide using liquid chromatography mass spectrometry.2. The method according to claim 1 , wherein the set of heavy C-terminal peptide standards comprises equimolar concentrations of Δ4 K peptide:Δ4 des-K peptide claim 1 , Δ8 K peptide:Δ4 des-K peptide claim 1 , Δ12 K peptide:Δ4 des-K peptide claim 1 , and Δ16 K peptide:Δ4 des-K peptide.3. The method of claim 2 , wherein the equimolar concentrations are at molar ratios of 1:1 claim 2 , 1:10 claim 2 , 1:100 claim 2 , and 1:1000 K peptide to des-K peptide.4. The method of claim 3 , wherein the K peptide standard is SEQ ID NO:2 and the des-K peptide standard is SEQ ID NO:1.5. The method of claim 3 , wherein the K peptide standard is SEQ ID NO:4 and the des-K peptide standard is SEQ ID NO:3.6. The method of claim 1 , wherein the percentage of K peptide is analyzed using liquid chromatography tandem mass spectrometry (LC-MS).7. The method of claim 4 , wherein the unprocessed C-terminal K is analyzed and quantified in a single LC-MSpeptide mapping run.8. The method of claim 1 , wherein the K peptide is an antibody.9. The method of claim ...

ANALYSIS METHOD AND NON-TRANSITORY COMPUTER READABLE MEDIUM

An analysis method includes analyzing a reference sample that contains a predetermined amount of a predetermined component by an analysis device using a chromatograph and obtaining a reference detection value which is a detection value of the predetermined amount of the predetermined component detected by the analysis device, calculating a judgment reference value which is a criterion for judging whether a concentration of a detection subject component in a measurement subject sample is equal to or larger than a reference concentration or equal to or smaller than the reference concentration based on the reference detection value, and analyzing the measurement subject sample by the analysis device and judging that the detection subject component has been detected in a case where a detection value exceeding the judgment reference value is detected in a peak detection time zone corresponding to the detection subject component. 1. An analysis method including:analyzing a reference sample that contains a predetermined amount of a predetermined component by an analysis device using a chromatograph and obtaining a reference detection value which is a detection value of the predetermined amount of the predetermined component detected by the analysis device;calculating a judgment reference value which is a criterion for judging whether a concentration of a detection subject component in a measurement subject sample is equal to or larger than a reference concentration or equal to or smaller than the reference concentration based on the reference detection value; andanalyzing the measurement subject sample by the analysis device and judging that the detection subject component has been detected in a case where a detection value exceeding the judgment reference value is detected in a peak detection time zone corresponding to the detection subject component.2. The analysis method according to claim 1 , whereindetection of the detection subject component or non-detection of the ...

METHODS FOR MICROBIAL IDENTIFICATION BY MASS SPECTROMETRY

Methods and systems for identification of microorganisms either after isolation from a culture or directly from a sample. The methods and systems are configured to identify microorganisms based on the characterization of proteins of the microorganisms via high-resolution/mass accuracy single-stage (MS) or multi-stage (MS) mass spectrometry. Included herein are also discussion of targeted detection and evaluation of virulence factors, antibiotic resistance markers, antibiotic susceptibility markers, typing, or other characteristics using a method applicable to substantially all microorganisms and high-resolution/mass accuracy single-stage (MS) or multi-stage (MS) mass spectrometry. 1. A method for identifying and characterizing one or more unknown microbes in a sample , the method comprising:a. performing a first analytical method using mass spectrometry to detect and identify one or more proteins from each of the one or more microbes;b. using the identity of the one or more proteins from each of the one or more microbes to assign a potential identity for at least one of the microbes in the sample to the genus species level;c. using information from step (b) to automatically select a second analytical method from a list of analytical methods, the second method also using mass spectrometry; wherein neither the first analytical method nor the second analytical method includes chemical or enzymatic digestion of the proteins; and', 'wherein further, at least the first analytical method is performed in real time., 'd. performing the second analytical method on the sample to further identify and, optionally, quantify, one or more proteins indicative of any of: strain and/or serovar identification, antimicrobial resistance, antimicrobial susceptibility and/or virulence, or any combination thereof;'}2. The method of claim 1 , wherein first analytical method includes mass spectrometry analysis of intact claim 1 , soluble proteins of the one or more microbes.3. The method of ...

Methods and compositions comprising reduced level of host cell proteins

The present disclosure pertains to compositions with reduced presence of host-cell proteins and methods of making such compositions. In particular, it pertains to compositions methods of making compositions with reduced presence of host-cell proteins from a host-cell.

Method for determining liver fat amount and method for diagnosing nafld

The present invention is based on the idea of determining certain molecular lipids from a subject's blood sample, for example from serum or plasma sample, and based on the amounts of the determined lipids determining the amount of liver fat and/or diagnosing NAFLD in the subject. More specifically the subjects with elevated liver fat amount and NAFLD are characterized by elevated triglycerides with low carbon number and double bond content in the blood sample. Lysophosphatidylcholines, ether phospholipids, sphingomyelins and PUFA-containing phospholipids are diminished in the blood samples of subjects with an elevated liver fat amount and NAFLD. The method of the present invention can be further used for monitoring the subject's response to the treatment of NAFLD or to the treatment of lowering of the liver fat amount in the subject.

NOVEL, HEAVY VITAMIN B12 DERIVATIVES

The invention discussed in this application relates to vitamin B12-based compounds that are useful as quantitative standards, particularly for the assessment of vitamin B12 deficiency. 1. A heavy vitamin B12 derivative having a mass shift of at least +7 over unlabelled vitamin B12 , wherein the heavy vitamin B12 derivative includes seven C atoms and the seven C atoms are located in the dimethylbenzimidazole moiety of the vitamin.24-. (canceled)5. The heavy vitamin B12 derivative of claim 1 , wherein the heavy vitamin B12 derivative has a mass shift of from +7 to +10 over unlabelled vitamin B12.6. The heavy vitamin B12 derivative of claim 5 , wherein the heavy vitamin B12 derivative has a mass shift of +7 over unlabelled vitamin B12.7. The heavy vitamin B12 derivative of claim 5 , wherein the heavy vitamin B12 derivative has a mass shift of +9 over unlabelled vitamin B12.10. The heavy vitamin B12 derivative of claim 1 , wherein the heavy vitamin B12 derivative further includes one or more H atoms.11. The heavy vitamin B12 derivative of claim 10 , wherein the heavy vitamin B12 derivative further includes two H atoms.12. A process for preparing a heavy vitamin B12 derivative according to claim 1 , the process including:{'sup': 13', '13, 'providing C-labelled 5,6-dimethylbenzimidazole having seven C atoms,'}providing cobinamide dicyanide,{'sup': '13', 'contacting the C-labelled 5,6-dimethylbenzimidazole with the cobinamide dicyanide in the presence of a bacterium,'}thereby producing the heavy vitamin B12 derivative.13. The process of claim 12 , wherein the C-labelled 5 claim 12 ,6-dimethylbenzimidazole has nine C atoms.14. The process of claim 12 , wherein the C-labelled 5 claim 12 ,6-dimethylbenzimidazole has one or more H atoms.15. The process of claim 14 , wherein the C-labelled 5 claim 14 ,6-dimethylbenzimidazole has two H atoms.16Salmonella entericaS. enterica. The process of claim 12 , wherein the bacterium is ().1718-. (canceled)19. The process of claim 12 , ...

METHOD FOR IDENTIFYING THE OAK SPECIES OF AN OAK WOOD SAMPLE

The invention concerns a method for identifying the oak species including the following steps of: Providing an oak wood sample; Preparing said sample; Performing at least one analysis on the wood sample so as: to identify: from one to three molecules belonging to a 1category of molecules defined by the derivatives of oleanane-type triterpenes which derive from an aglycone of empirical formula CHO, from one to three molecules belonging to a 2category of molecules defined by the derivatives of oleanane-type triterpenes which derive from an aglycone of empirical formula CHO, as well as derivatives of oleanane-type triterpenes which derive from an aglycone of empirical formula CHO, then to determine the concentration of the identified molecules; Determining a ratio R; Identifying the oak species. 1. A method for identifying the oak species of an oak wood sample , comprises at least the following steps of:a) Providing an oak wood sample;b) Preparing the oak wood sample in a suitable manner for an analysis for determining the concentration of derivatives of oleanane-type triterpenes which are present in said oak wood sample; [ [{'sup': st', 'st', 'st, 'sub': 30', '48', '6, 'i. from one to three molecules belonging to a 1category of molecules, said one to three molecules being among the three most abundant molecules of all the molecules of said 1category of molecules present in said oak wood sample, said 1category of molecules being defined by all derivatives of oleanane-type triterpenes which derive from an aglycone of empirical formula CHO,'}, {'sup': nd', 'nd', 'nd, 'sub': 30', '46', '7', '30', '46', '8, 'ii. from one to three molecules belonging to a 2category of molecules, said one to three molecules being among the three most abundant molecules of all the molecules of said 2category of molecules present in said oak wood sample, said 2category of molecules being defined by all derivatives of oleanane-type triterpenes which derive from an aglycone of empirical formula ...

DIFFERENTIAL DIAGNOSIS OF LIVER DISEASE

The disclosure relates to the substantially non-invasive diagnosis of liver disease, especially to enable intervention in the progression of such disease at an early stage. This invention further relates to the use of plasma biomarkers to differentiate nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver (NAFL) and non-nonalcoholic fatty liver disease (NAFLD), and normal controls. Specifically, the invention relates to the use of free eicosanoids and other polyunsaturated fatty acid (PUFA) metabolite levels in plasma to differentiate NASH from NAFL and non-NAFLD normal controls. 1. A substantially non-invasive method of predicting or assessing the risk of progression of liver disease in a patient diagnosed with liver disease comprising:directly treating a plasma sample from a subject with alcohol to dissolve free eicosanoids and free polyunsaturated fatty acid (fPUFA) to obtain free-dissolved eicosanoids and free-dissolved fPUFAs;purifying the free-dissolved eicosanoids and free-dissolved fPUFAs;measuring the level of eicosanoids and/or PUFA metabolites selected from the group consisting of (i) dhk PGD2, (ii)20-COOH AA, (iii) 11,12-diHETrE and dhk PGD2;(iv) 11,12-diHETrE and 20-COOH AA; (v) dhk PGD2 and 20-COOH AA and (vi) dhk PGD2, 20-COOH AA and 11,12-diHETrE, and one or more additional compounds selected from the group consisting of PGE2, tetranor 12-HETE, 15-HETE, 14,15-diHETrE, 9-oxoODE and 12,13 EpOME;determining the area under receiver operating characteristic curve (AUROC) based upon a ratio of the levels of the free-dissolved eicosanoids and/or free-dissolved fPUFA metabolites matched with deuterated internal standards of the same metabolite.2. The method of claim 1 , wherein the liver disease is a nonalcoholic fatty liver disease (NAFLD).3. The method of claim 2 , wherein the NAFLD is nonalcoholic steatohepatitis (NASH).4. The method of claim 1 , wherein the ratio or a converted absolute value amount is communicated to a physician.5. The ...

APPARATUS AND METHODS FOR PLASMA-ASSISTED REACTION CHEMICAL IONIZATION (PARCI) MASS SPECTROMETRY

Plasma-assisted reaction chemical ionization (PARCI) provides highly sensitive elemental analysis by producing positively and negatively charged ions. The PARCI apparatuses, kits, and methods described in this application relate to systems that comprise a chemical reaction interface (CRI) containing reactant gas plasma and an ionization chamber that is downstream from the CRI. The ionization chamber facilitates formation of ions from element-specific products of the CRI by an electron source or an ionization gas. In particular, PARCI provides a method for conducting highly sensitive mass spectrometric elemental analysis of analyte compounds with high ionization potential elements; for example, fluorine, chlorine, and bromine. 1. An apparatus for elemental mass spectrometry comprising:a chemical reaction interface (CRI), which comprises reactant gas plasma; 'wherein the ionization chamber is downstream of the CRI; and', 'an ionization chamber,'}a mass-spectrometer.2. The apparatus of claim 1 , wherein the ionization chamber comprises an electron source.3. The apparatus of claim 1 , wherein the ionization chamber comprises an ionization gas and/or a dopant molecule.4. The apparatus of claim 1 , wherein the pressure in the ionization chamber is greater than about 1.0 torr.5. The apparatus of claim 1 , wherein the plasma reactant gas comprises helium (He) claim 1 , nitrogen (N) claim 1 , argon (Ar) claim 1 , oxygen (O) claim 1 , hydrogen (H) claim 1 , air claim 1 , water or a combination thereof.6. The apparatus of claim 1 , wherein the plasma is at a pressure of between about 1.0 torr to about 50.0 torr.7. The apparatus of claim 1 , wherein the plasma is at atmospheric pressure.8. The apparatus of claim 3 , wherein the dopant or ionization gas is acetone claim 3 , toluene claim 3 , benzoic acid claim 3 , nitrogen (N) claim 3 , oxygen claim 3 , ammonia (NH) claim 3 , air claim 3 , argon (Ar) methanol claim 3 , water claim 3 , or a combination thereof.9. The apparatus of ...

MASS SPECTROMETER

Provided is a mass spectrometer which repeats the operation of capturing ions originating from a sample component into an ion trap (), ejecting the ions from the ion trap, and analyzing the ions with a TOF mass analyzer (). A capturing voltage generator () applies an ion-capturing radio-frequency voltage to the ion trap. An ejecting voltage generator () applies an ion-ejecting voltage whose phase is synchronized with the radio-frequency voltage. A controller () controls those devices to introduce next ions to be analyzed into the ion trap while performing a mass spectrometric analysis in the TOF mass analyzer. A blank signal acquirer () acquires a blank signal within a measurement period or measurement window while the ion trap is being operated. A noise remover () subtracts blank-signal data from signal intensity data acquired by a sample measurement. A spectrum creator () creates a mass spectrum based on noise-removed data. 1. A mass spectrometer including an ion trap configured to capture an ion by a radio-frequency electric field and a time-of-flight mass analyzer configured to perform a mass spectrometric analysis on an ion ejected from the ion trap , the mass spectrometer configured to repeatedly perform an operation of capturing an ion originating from a sample component into the ion trap , ejecting the ion from the ion trap and analyzing the ion with the time-of-flight mass analyzer , and the mass spectrometer comprising:a capturing voltage generator configured to apply an ion-capturing radio-frequency voltage to at least one of the electrodes forming the ion trap;an ejecting voltage generator configured to apply an ion-ejecting voltage to at least one of the electrodes forming the ion trap, where a phase of the ion-ejecting voltage is synchronized with a phase of the radio-frequency voltage;a controller configured to control the capturing voltage generator and the ejecting voltage generator so as to introduce an ion to be subsequently analyzed into the ion ...

Method of evaluating quality of dephosphorylation reagent and method of detecting target nucleic acid

A method evaluates a quality of a dephosphorylation reagent, the method including the steps of: providing a dephosphorylation reagent containing an alkaline phosphatase and a peptide fragment derived from the alkaline phosphatase; and evaluating the dephosphorylation reagent as having a high quality if a content ratio of the peptide fragment to the alkaline phosphatase is a predetermined reference value or less.

MATERIALS FOR HYDROPHILIC INTERACTION CHROMATOGRAPHY AND PROCESSES FOR PREPARATION AND USE THEREOF FOR ANALYSIS OF GLYCOPROTEINS AND GLYCOPEPTIDES

The invention relates to poly-amide bonded hydrophilic interaction chromatography (HILIC) stationary phases and novel HILIC methods for use in the characterization of large biological molecules modified with polar groups, known to those skilled in the art as glycans. The invention particularly provides novel, poly-amide bonded materials designed for efficient separation of large biomolecules, e.g. materials having a large percentage of larger pores (i.e. wide pores). Furthermore, the invention advantageously provides novel HILIC methods that can be used in combination with the stationary phase materials described herein to effectively separate protein and peptide glycoforms by eliminating previously unsolved problems, such as on-column aggregation of protein samples, low sensitivity of chromatographic detection of the glycan moieties, and low resolution of peaks due to restricted pore diffusion and long intra/inter-particle diffusion distances. 149-. (canceled)50. A method for analyzing a glycosylated proteinaceous sample , comprising contacting the sample with a chromatographic material in the presence of a mobile phase eluent to thereby analyze the sample , wherein the chromatographic material is a porous material which comprises at least one hydrophilic monomer and a poly-amide bonded phase.51. The method of claim 50 , wherein an average pore diameter of the porous material is greater than or equal to about 200 Å.52. The method of claim 50 , wherein an average pore diameter of the porous material is ranges from about 200 Å to about 450 Å.53. The method of claim 50 , wherein the porous material has an average pore diameter of about 300 Å.54. The method of claim 50 , wherein the mobile phase eluent is a high organic eluent.55. The method of claim 50 , wherein the mobile phase eluent comprises acetonitrile claim 50 , isopropanol claim 50 , n-propanol claim 50 , methanol claim 50 , ethanol claim 50 , butanol claim 50 , water claim 50 , or a mixture thereof.56. The ...

METHODS OF DETECTING REVERSE TRIIODOTHYRONINE BY MASS SPECTROMETRY

Provided are methods for determining the amount of reverse T3 in a sample using mass spectrometry. The methods generally involve ionizing reverse T3 in a sample and detecting and quantifying the amount of the ion to determine the amount of reverse T3 in the sample. 1. A method for determining the amount of reverse triiodothyronine (rT3) in a sample by mass spectrometry , said method comprising:a. ionizing rT3 from the sample to generate one or more rT3 ions detectable by mass spectrometry, wherein ionizing is by electrospray ionization (ESI);b. determining the amount of one or more rT3 ions by mass spectrometry; andc. determining the amount of rT3 in the body fluid sample from the amount of said rT3 ions determined in (b).2. The method of claim 1 , further comprising subjecting the rT3 from the sample to liquid chromatography prior to ionizing.3. The method of claim 2 , wherein liquid chromatography comprises high performance liquid chromatography (HPLC) claim 2 , reverse phase liquid chromatography (RPLC) claim 2 , reverse-phase high performance liquid chromatography (RP-HPLC) claim 2 , or high turbulence liquid chromatography (HTLC).4. The method of claim 2 , further comprising subjecting the sample to protein precipitation prior to liquid chromatography.5. The method of claim 4 , wherein said protein precipitation comprises organic solvent precipitation.6. The method of claim 4 , wherein said protein precipitation comprises methanol precipitation.7. The method of claim 1 , wherein said mass spectrometry is tandem mass spectrometry.8. The method of claim 1 , wherein further comprising enriching rT3 in the sample.9. The method of claim 8 , wherein enriching comprises liquid chromatography claim 8 , filtration claim 8 , centrifugation claim 8 , thin layer chromatography (TLC) claim 8 , electrophoresis including capillary electrophoresis claim 8 , affinity separations including immunoaffinity separations claim 8 , or extraction.10. The method of claim 1 , wherein ...

Analysis System

An analysis system is provided with: a storage unit that stores first information associating mass spectrometry result information with an analysis condition concerning ion mobility separation; and a control unit that determines, as a first analysis condition for an ion to be measured, the analysis condition associated with the mass spectrometry result information of the first information corresponding to the mass spectrometry result information of the ion to be measured. 1. An analysis system comprising:a storage unit that stores first information associating mass spectrometry result information with an analysis condition concerning ion mobility separation; anda control unit that determines, as a first analysis condition for an ion to be measured, the analysis condition associated with the mass spectrometry result information of the first information corresponding to the mass spectrometry result information of the ion to be measured.2. The analysis system according to claim 1 , wherein:the mass spectrometry result information of the ion to be measured includes a mass-to-charge ratio and a charge;the storage unit stores second information associating the mass-to-charge ratio with a separation voltage; andthe control unit determines, as the first analysis condition, a first separation voltage associated with the mass-to-charge ratio of the second information corresponding to the mass-to-charge ratio of the ion to be measured.3. The analysis system according to claim 2 , wherein:the control unit determines, in the absence of the mass spectrometry result information of the first information corresponding to the mass spectrometry result information of the ion to be measured, the first separation voltage in the second information as the first analysis condition; andthe control unit stores the first analysis condition in the storage unit as the first information.4. The analysis system according to claim 2 , wherein:the control unit scans a plurality of compensation ...

System and method for the detection of allergens

Methods and systems for detecting allergens using mass spectrometry are provided herein. In some aspects, a sample can be screened for the presence or quantity of ovalbumin, lysozyme, casein (isoform S1 and S2), lactoglobulin, high and low glutens, wheat, rye, oats, barley, mustard, sesame, and various types of nuts including macadamia, pistachio, brazil, walnuts, peanuts and hazelnuts by detecting one or more peptides specific to the allergen of interest using selected MRM transitions.

QUANTITATION OF TAMOXIFEN AND METABOLITES THEREOF BY MASS SPECTROMETRY

Provided are methods for determining the amount of tamoxifen and its metabolites in a sample by mass spectrometry. In some aspects, the methods provided herein determine the amount of norendoxifen. In some aspects, the methods provided herein determine the amount of norendoxifen and tamoxifen. In some aspects, the methods provided herein determine the amount of norendoxifen and other tamoxifen metabolites. In some aspects, the methods provided herein determine the amount of tamoxifen, norendoxifen, and other tamoxifen metabolites. 1. A method for determining the amount of norendoxifen in a human sample by mass spectrometry , comprising:(a) purifying the sample by liquid chromatography;(b) ionizing said norendoxifen to produce one or more norendoxifen ions detectable by mass spectrometry;(c) detecting the amount of the norendoxifen ion(s) from step (b) by mass spectrometry;wherein the amount of the ion(s) detected is related to the amount of norendoxifen in said sample,wherein the method has a limit of quantitation of less than or equal to 5 ng/mL.2. The method of claim 1 , further comprising protein precipitation prior to step (a).3. The method of claim 1 , further comprising filtration prior to step (a).4. The method of claim 1 , wherein said liquid chromatography is high pressure liquid chromatography (HPLC).5. The method of claim 1 , wherein said liquid chromatography is high turbulence liquid chromatography (HTLC).6. The method of claim 1 , further comprising detecting the amount of an internal standard.7. The method of claim 5 , wherein said internal standard is a N-Desmethyl-4-Hydroxy Tamoxifen-d5.8. The method of claim 1 , wherein said ionization is by atmospheric pressure chemical ionization (APCI).9. The method of claim 1 , wherein said ionization is by electrospray ionization (ESI).10. The method of claim 1 , wherein said ionization is in positive ion mode.11. The method of claim 1 , wherein said sample is a serum or plasma sample.12. The method of claim 1 ...

IDENTIFICATION OF BLOOD BASED METABOLITE BIOMARKERS OF PANCREATIC CANCER

The present disclosure relates to a panel of a plurality of metabolite species that is useful for the identification or detection of subjects having pancreatic cancer, including methods for identifying such metabolic biomarkers within biological samples. The disclosure also includes a statistical model for predicting the presence of pancreatic cancer in a subject's biofluid by quantifying and comparing positive and negative fold changes in metabolite species' concentration; comparing the subject's metabolite species' concentrations to a predetermined value. 1establishing a training dataset based on measured concentrations of at least two metabolite species based on known pancreatic cancer data, wherein the at least two metabolite species is a component of a panel of a plurality of metabolite species;measuring concentrations of the at least two metabolite species in a sample of a biofluid from a subject;comparing the measured concentration of the at least two metabolite species to the training dataset based on combined regression and univariate analysis, thereby generating a score; andcomparing the score to a score of healthy group in order to predict presence of pancreatic cancer in the subject.. A method for detecting pancreatic cancer in a subject, comprising: The present application is a continuation of U.S. application Ser. No. 14/465,535, filed Aug. 21, 2014, which claims the benefit of U.S. provisional application Ser. No. 61/868,398, filed Aug. 21, 2013, the contents of which are incorporated by reference herein in their entirety.The present disclosure generally relates to small molecule metabolic biomarkers. In particular, the present disclosure relates to a panel of metabolite species that is useful for the identification of subjects having pancreatic cancer, including methods for identifying such metabolic biomarkers within biological samples.Pancreatic cancer (PC) afflicts both men and women, and is the fourth leading cause of cancer related deaths in the ...

METHOD FOR IDENTIFYING AND ANALYZING DISSOLVED ORGANIC NITROGEN OF DIFFERENT SOURCES IN WASTEWATER AND APPLICATION OF THE METHOD

A method for identifying and analyzing dissolved organic nitrogen of different sources in wastewater includes extracting DON in wastewater to obtain a DON extract, detecting mass spectrum peaks in the DON extract, pre-processing the spectral data of the wastewater sample; constructing a network relationship of the substance reaction in the wastewater sample; screening the substance reaction relationship of DON; and determining different sources of DON. 1. A method for identifying and analyzing dissolved organic nitrogen of different sources in wastewater , the method comprising:a) separating dissolved organic nitrogen (DON) from interferents of a wastewater sample through operations comprising pretreatment of the wastewater sample, column activation, sample loading, leaching, and elution using solid phase extraction cartridges (SPE cartridges), concentrating and enriching DON in the wastewater sample, to obtain a DON extract;b) performing full scan analysis and detection of the DON extract using a liquid chromatography-high resolution mass spectrometer (LC-HRMS), to obtain a detection spectrum of DON in the wastewater sample;c) performing subtraction of background signal values, elimination of interference peaks, and elimination of noise signals from the detection spectrum of DON in the wastewater sample, to obtain preprocessed spectral data of the wastewater sample;d) performing extraction of peaks of the spectral data of the wastewater sample, hierarchical clustering of a retention time of peaks of the spectral data, and peak de-redundancy of the wastewater sample using a reaction omics analysis technology, to simplify the spectral data of the wastewater sample;establishing a global reaction quality difference relationship, screening independent mass spectrum peaks, and constructing a high-frequency mass difference matrix of a substance reaction in the wastewater sample; combining the high-frequency mass difference matrix and a substance reaction database to ...

Method and System of Identifying and Quantifying A Protein

Methods and system for identifying and/or quantifying a protein are provided herein.

VITAMIN D METABOLITE DETERMINATION UTILIZING MASS SPECTROMETRY FOLLOWING DERIVATIZATION

The invention relates to the detection of vitamin D metabolites. In a particular aspect, the invention relates to methods for detecting derivatized vitamin D metabolites by mass spectrometry. 1. A method for determining an amount of one or more vitamin D metabolites in a sample by mass spectrometry , the method comprising:(i) adding one or more internal standards to a sample;(ii) precipitating one or more vitamin D metabolites and one or more internal standards with acetonitrile;(iii) subjecting the one or more vitamin D metabolites and one or more internal standards to 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) derivatization;(iv) subjecting the one or more vitamin D metabolites and one or more internal standards to solid phase extraction (SPE);(v) ionizing the one or more PTAD-derivatized vitamin D metabolites derivatives and the one or more PTAD-derivatized internal standards; and(vi) determining an amount of the one or more PTAD-derivatized vitamin D metabolites and the one or more PTAD-derivatized internal standards by mass spectrometry, wherein the amount of the one or more PTAD-derivatized vitamin D metabolites is determined from the amount of ions from step (v).2. The method of claim 1 , wherein the one or more vitamin D metabolites is dihydroxy vitamin D.3. The method of claim 1 , wherein the one or more vitamin D metabolites comprise at least one of 1α claim 1 ,25-dihydroxyvitamin D(1α claim 1 ,25(OH)D) and 1α claim 1 ,25-dihydroxyvitamin D(1α claim 1 ,25(OH)D).4. The method of claim 1 , wherein the internal standard comprises 1α claim 1 ,25(OH)D-[6 claim 1 , 26 claim 1 , 26 claim 1 , 27 claim 1 , 27 claim 1 , 27]-H.5. The method of claim 1 , wherein the internal standard comprises 1α claim 1 ,25(OH)D-[6 claim 1 , 19 claim 1 , 19]-H.6. The method of claim 1 , wherein the sample is a plasma or serum.7. The method of claim 1 , wherein the mass spectrometry is tandem mass spectrometry.8. The method of claim 1 , further comprising subjecting the one or more ...

ANALYTICAL METHODS FOR ANALYZING AND DETERMINING IMPURITIES IN DIANHYDROGALACTITOL

An improved analytical method for analysis of dianhydrogalactitol preparations provides a method for determining the purity of dianhydrogalactitol and detecting impurities in preparations of dianhydrogalactitol, as well as identifying any such impurities. The method employs high performance liquid chromatography (HPLC), in particular, HPLC with refractive index (RI) detection; the HPLC can be followed by tandem mass spectroscopy. The method can further comprise the step of performing preparative HPLC collection of at least one specific substance peak present in a preparation of dianhydrogalactitol. 1. An analytical method for analyzing the presence and quantity of impurities present in a preparation of dianhydrogalactitol comprising the steps of:(a) analyzing a preparation of dianhydrogalactitol by subjecting the preparation to high performance liquid chromatography using elution with a mobile phase gradient to separate dianhydrogalactitol from dulcitol and other contaminants of the preparation; and(b) determining the relative concentration of one or more peaks resolved by high performance liquid chromatography that represent compounds other than dianhydrogalactitol itself.2. The method of wherein the compounds other than dianhydrogalactitol itself are at least one of: (1) dulcitol; (2) an impurity other than dulcitol; and (3) a degradation product of dianhydrogalactitol.3. The analytical method of wherein elution is with a gradient of NaOH from about 2.5 mM to about 0.1 mM.4. The analytical method of wherein elution is with a gradient of NaOH from about 1.5 mM to about 0.1 mM.5. The analytical method of wherein elution is with a gradient of NaOH from about 1 mM to about 0.1 mM.6. The analytical method of wherein elution is with a gradient of a combination of ammonium hydroxide and a volatile ammonium salt selected from the group consisting of ammonium formate and ammonium acetate and the total concentration of the ammonium hydroxide and the volatile ammonium salt ...

Mass spectrometer

Under the control of a DDA (data dependent acquisition) execution controller (281), LC/MSn analysis data are acquired with a measurement unit (1) and stored in a measurement data storage section (23). In the case where the MSn analysis is automatically performed, a precursor ion intensity, TIC value and BPC value are also stored and related to the measurement data. In an analysis of the data, a spectrum display condition setter (25) displays, on a display unit (4), a setting window for allowing an analysis operator to enter a precursor ion intensity threshold as well as a product ion intensity threshold which is either the TIC or BPC value, and stores the entered values as a judgment condition in a spectrum display condition storage section (26). When an appropriate retention time is specified on a chromatogram displayed on the screen of the display unit (4), and if MSn spectrum data has already been acquired at that retention time, a spectrum judgment section (27) determines whether or not the precursor ion intensity and other relevant data related to the MSn spectrum data satisfy the judgment condition and selectively displays, on the screen of the display unit (4), only MSn spectra that satisfy the judgment condition. By this operation, useless MSn spectra with low ion intensities are excluded from the display.

Mass Spectrometry Analysis of Mutant Polypeptides in Biological Samples

The invention relates to a method for determining the presence of at least one distinct polypeptide in a biological sample comprising contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct polypeptide in a sequence-specific manner such that at least one distinct peptide having a predetermined peptide measured accurate mass would result if the at least one distinct polypeptide were present in the biological sample, to obtain a hydrolyzed sample; bringing the hydrolyzed sample in contact with a substrate comprising at least one immobilized binding partner, wherein the at least one immobilized binding partner is capable of specifically binding the distinct peptide; removing the hydrolyzed sample from the substrate in a manner such that the distinct peptide would remain bound to the immobilized binding partner; contacting the substrate with an elution solution, wherein the distinct peptide would dissociate from the immobilized binding partner into the elution solution; subjecting a portion of the elution solution to liquid chromatography to segregate a plurality of molecules in the portion of the elution solution to obtain sorted molecules; determining the measured accurate mass of at least one sorted molecule present in the elution solution; and determining the presence of the at least one distinct polypeptide in the biological sample when a measured accurate mass of at least one molecule is substantially equal to the predetermined peptide measured accurate mass. 128.-. (canceled)29. A method for determining the presence of at least one distinct polypeptide in a biological sample , wherein the at least one distinct polypeptide contains a mutation or post-translational modification relative to a wild type or unmodified polypeptide , respectively , the method comprising:(a) contacting the biological sample with a hydrolyzing agent, wherein the hydrolyzing agent is capable of hydrolyzing the distinct ...

SYSTEM AND METHOD FOR GROUPING PRECURSOR AND FRAGMENT IONS USING SELECTED ION CHROMATOGRAMS

LC/MS data generated by an LC/MS system is analyzed to determine groupings of ions associated with originating molecules. Ions are grouped initially according to retention time, for example, using retention time or chromatographic peaks in mass chromatograms. After initial groupings are determined based on retention time, ion peak shapes are compared to determine whether ions should be excluded. Ions having peak shapes not matching other ions, or alternatively a reference peak shape, are excluded from the group. 120-. (canceled)21. A method of LC/MS analysis of a complex sample , comprising:collecting LC/MS data using multiple alternating cycles of high-energy and low-energy fragmentation within a time scale of a chromatographic peak to obtain spectra from high-energy fragment ions and low-energy precursor ions associated with an originating molecule of the complex sample, wherein each of the ions of the spectra has a chromatographic retention time and a peak profile; andgrouping precursor ions and fragment ions that derive from a common originating molecule in response to a correspondence in the chromatographic retention times and one or more characteristics of the peak profiles of the precursor ions and fragment ions.22. The method of claim 21 , wherein the one or more characteristics of the peak profiles includes a peak shape symmetry.23. The method of claim 21 , wherein the one or more characteristics of the peak profiles includes an apex retention time.24. The method of claim 21 , wherein the one or more characteristics of the peak profiles includes a peak width.25. The method of claim 21 , wherein the one or more characteristics of the peak profiles includes a lift off time of initial detection.26. The method of claim 21 , wherein the one or more characteristics of the peak profiles includes a touch down time of final detection.27. The method of claim 21 , wherein the one or more characteristics of the peak profiles includes a normalized slope.28. The method ...

VALVE AND SPLITTING SYSTEM FOR MULTI-DIMENSIONAL LIQUID ANALYSIS

A multi-dimensional liquid analysis system includes a flow splitter for separating mobile phase outflow from a first dimension liquid analysis system into first and second liquid split outlet flows. Volumetric flow rate control of the split outlet flows is provided by a flow control pump which withdraws one of the split outlet flows from the flow splitter at a controlled withdrawal flow rate to define the other split outlet flow rate as the difference between the outflow rate from the first dimension system and the withdrawal flow rate. In this manner, accurate and consistent flow division can be accomplished, which is particularly useful for multi-dimensional liquid analysis. 1. A multi-dimensional liquid analysis system , comprising:a first separation system including a first separation column, the first separation column configured to chromatographically separate a sample within a liquid mobile phase and to provide a first dimension outflow having a first outflow rate;a flow splitter fluidly coupled to the first dimension outflow, the flow splitter configured to split the first dimension outflow into a first split outlet flow and a second split outlet flow;a second separation system including a sample loop and a second separation column, wherein the second separation system is configured such that the sample loop receives a sample volume from the second split outlet flow, and wherein the second separation column is configured to chromatographically separate the sample volume from the second split outlet flow; anda flow controller fluidly coupled to and located downstream of one of the first split outlet flow and the second split outlet flow, the flow controller configured to control the flow rate of the one of the first split outlet flow and the second split outlet flow from the flow splitter at a controlled flow rate to obtain, in the sample volume from the second split outlet flow, a representative sampling of compounds in the first dimension outflow for ...

SMALL MOLECULE BIOCHEMICAL PROFILING OF INDIVIDUAL SUBJECTS FOR DISEASE DIAGNOSIS AND HEALTH ASSESSMENT

Methods and systems are described herein for small molecule biochemical profiling of an individual subject for diagnosis of a disease or disorder, facilitating diagnosis of a disease or disorder, and/or identifying an increased risk of developing a disease or disorder in the individual subject. Aberrant levels of small molecules present in a sample from an individual subject are identified and diagnostic information relevant to the individual subject is obtained based on the identified aberrant levels. The obtained diagnostic information includes one or more of an identification of at least one biochemical pathway associated with the identified subset of the small molecules having aberrant levels, an identification at least one disease or disorder associated with the identified subset of the small molecules having aberrant levels, and an identification of at least one recommended follow up test associated with the identified subset of the small molecules having aberrant levels. 1. (canceled)2. A system for measuring levels of small molecules in a sample from an individual subject to determine small molecules having aberrant levels in the sample from the individual subject , the system comprising: a determination of relative levels of small molecules in a reference sample from a reference subject, for each of a plurality of reference samples from a corresponding plurality of reference subjects, during a first experimental run; and', 'a determination of relative levels of small molecules in the sample from the individual subject during a second experimental run that is separate from the first experimental run and in which experimental data is also generated from one or more anchor sample(s) before or after generation of the experimental data from the sample from the individual subject, wherein the anchor sample(s) include aliquots from the reference samples from the plurality of reference subjects; and, 'a) a mass spectrometer system configured to obtain experimental ...

Peptide quantitation assay for differentiating full-length high molecular weight kininogen (hmwk) and cleaved hmwk

Methods for differentiating full-length high molecular weight kininogen (HMWK) and cleaved HMWK in a sample are provided herein. Such methods may comprise treating a biological sample with a protease to generate a plurality of digested peptides, and measuring one or more signature peptides, which are indicative of cleaved HMWK and/or full-length HMWK.

AFFINITY CHROMATOGRAPHY-COUPLED NATIVE MASS SPECTROMETRY FOR ANTIBODY ANALYSIS

The present invention provides rapid, sensitive high-throughput methods and systems for characterizing peptides or proteins using affinity-based chromatography-coupled native mass spectrometry to improve manufacturing process of biopharmaceutical products, such as identifying impurities during antibody purification, monitoring post-translational modification variants during production, or characterizing drug-to-antibody ratio of antibody-drug conjugates. The separation profiles of the peptides or proteins are generated and compared to identify or qualify the peptides or proteins, wherein the separation profile is based on differential affinity binding. 1. A method for identifying at least one peptide or protein in a sample , comprising:contacting the sample to a solid surface, wherein the solid surface comprises an affinity-binding molecule of the at least one peptide or protein;washing the solid surface using a mobile phase to produce at least one eluent, wherein the eluent comprises the at least one peptide or protein; andcharacterizing the at least one peptide or protein in the at least one eluent using a mass spectrometer under native conditions.2. The method of claim 1 , further comprising generating at least one separation profile.3. The method of claim 2 , further comprising identifying or quantifying the at least one peptide or protein based on the at least one separation profile.4. The method of claim 2 , further comprising identifying or quantifying a level of post-translational modification or post-translational modification variation of the at least one peptide or protein based on the at least one separation profile or a comparison with another separation profile.5. The method of claim 2 , further comprising identifying or quantifying a level of glycosylation or glycosylation variation of the at least one peptide or protein based on the at least one separation profile or a comparison with another separation profile.6. The method of claim 5 , wherein the ...

2-AAA as a Biomarker and Therapeutic Agent for Diabetes

Methods for treating a glucose-related metabolic disorder (e.g., diabetes) comprising administration of 2-aminoadipic acid (2-AAA) to subjects in need thereof. Also described are methods for predicting a subject's risk of developing a glucose-related metabolic disorder, and to methods for selecting and monitoring a treatment for a glucose-related metabolic disorder (e.g., diabetes). 19.-. (canceled)10. A method for determining risk of developing diabetes in a subject , the method comprising:determining a level of 2-aminoadipic acid (2-AAA) in a test sample from the subject;comparing the level of 2-AAA in the test sample to a reference level; anddetermining the subject has an increased risk of developing diabetes when the test sample has an increased level of 2-AAA as compared to the reference level.11. The method of claim 10 , wherein the test sample comprises serum or plasma from the subject.12. The method of claim 10 , wherein the subject has normal glucose tolerance.13. The method of claim 10 , further comprising selecting a treatment based on the level of 2-aminoadipic acid in the test sample.14. The method of claim 13 , further comprising administering the selected treatment to the subject.15. The method of claim 13 , wherein the treatment comprises administering to the subject an effective amount of at one or more additional anti-diabetes compound selected from the group consisting of acarbose claim 13 , miglitol claim 13 , metformin claim 13 , phenformin claim 13 , buformin claim 13 , repaglinide claim 13 , nateglinide claim 13 , tolbutamide claim 13 , chlorpropamide claim 13 , tolazamide claim 13 , acetohexamide claim 13 , glyburide claim 13 , glipizide claim 13 , glimepiride claim 13 , gliclazide claim 13 , troglitazone claim 13 , rosiglitazone claim 13 , pioglitazone claim 13 , peptide analogs claim 13 , glucagon-like peptide I (GLP1) and analogs thereof claim 13 , GLP agonists claim 13 , vildagliptin sitagliptin; dichloroacetic acid; amylin claim 13 , ...

Methods for determining total body skeletal muscle mass

The present invention is based on the finding that enrichment of D3-creatinine in a urine sample following oral administration of a single defined dose of D3-creatine can be used to calculate total-body creatine pool size and total body skeletal muscle mass in a subject. The invention further encompasses methods for detecting creatinine and D3-creatinine in a single sample. The methods of the invention find use, inter alia, in diagnosing disorders related to skeletal muscle mass, and in screening potential therapeutic agents to determine their effects on muscle mass.

MASS ANALYSIS DATA PROCESSING APPARATUS AND MASS ANALYSIS DATA PROCESSING METHOD

To enhance the efficiency in the operation of checking a plurality of mass spectra acquired by measuring MS(n is an integer equal to or more than two) of a sample containing an unidentified component under a plurality of measurement conditions. A mass analysis data processing apparatus for processing data constituting a plurality of mass spectra acquired by performing MS(n is an integer equal to or more than two) measurement of an unidentified component contained in a sample under a plurality of different measurement conditions, the apparatus including: a determination condition input unit for allowing an analyst to input a determination condition concerning a maximum intensity value of mass peaks on the mass spectra, in order to select, out of the plurality of mass spectra, a mass spectrum or mass spectra effective for presuming the unidentified component; a determination execution unit for determining whether or not the determination condition is satisfied in each of the plurality of mass spectra; and a selection result presentation unit for selecting a mass spectrum or mass spectra, determined to satisfy the determination condition by the determination execution unit , and presenting the mass spectrum or spectra to the analyst. 1. A mass analysis data processing apparatus for processing data constituting a plurality of mass spectra acquired by performing MS(n is an integer equal to or more than two) measurement of an unidentified component contained in a sample under a plurality of different measurement conditions , the apparatus comprising:a) a determination condition input unit for allowing an analyst to input a determination condition concerning a maximum intensity value of mass peaks on the mass spectra, in order to select, out of the plurality of mass spectra, a mass spectrum or mass spectra effective for presuming the unidentified component;b) a determination execution unit for determining whether or not the determination condition is satisfied in each of ...

MASS SPECTROMETRY METHOD, CHROMATOGRAPH MASS SPECTROMETER, AND PROGRAM FOR MASS SPECTROMETRY

A mass spectrometry method includes: creating a plurality of measurement conditions corresponding to all combinations of precursor-ion candidates generated from the target compound and collision-energy-value candidates; performing a product-ion scan measurement using each of the plurality of measurement conditions and performing a plurality of reference measurements for detecting a predetermined kind of ion generated from the target compound under the same condition, within an introduction time during which the target compound is introduced; creating a peak function, which is a function representing a change in the amount of introduction of the target compound into the mass spectrometer within the introduction time, based on the result of the reference measurement; creating a normalization function for normalizing the amount of introduction of the target compound within the introduction time, based on the peak function; and normalizing the intensity of product-ion spectra obtained by the product-ion scan measurements performed for all combinations. 1. A mass spectrometry method for optimizing a condition of a multiple reaction monitoring measurement of a target compound contained in a sample using a chromatograph mass spectrometer including a chromatograph and a mass spectrometer having front and rear mass separators with a collision cell in between , the method comprising:a) creating a plurality of measurement conditions corresponding to all combinations of one or more precursor-ion candidates generated from the target compound and one or more collision-energy-value candidates;b) introducing the sample into the chromatograph mass spectrometer;c) performing a product-ion scan measurement at least one time using each of the plurality of measurement conditions as well as performing, a plurality of times and under a same condition, a reference measurement for detecting a predetermined kind of ion generated from the target compound, within an introduction time during ...

MULTI-DIMENSIONAL CHROMATOGRAPH SYSTEM

In a two-dimensional LC system configured to introduce components trapped in a trap column during a fractionation period T into a second-dimension column, separate components, and then detect the components using a mass spectrometer, a data collection unit receives a signal which indicates timing to delimit the fractionation period T, determines the first data item in the fractionation period T, adds measurement start point identification information to the first data item, and stores all the data in a data storage unit. A two-dimensional chromatogram creation unit recognizes the first data item in each fractionation period T from the read data, and create a two-dimensional chromatogram by aligning data so that the first data items will be aligned at the top along an abscissa. 1. A multi-dimensional chromatograph system comprising: an (n−1)th-dimension column (where n is an integer equal to or larger than 2) configured to chronologically separate a plurality of components contained in a sample; a holding unit configured to hold components of the sample , the components being obtained from the (n−1)th-dimension column within a predetermined time period; an nth-dimension column configured to further chronologically separate components of the sample held by the holding unit; and a detection unit configured to detect the components of the sample in sequence , the components being obtained from the nth-dimension column , wherein the components of the sample obtained from the (n−1)th-dimension column are fractionated at every predetermined time period and held by the holding unit , and an operation in which the components held by the holding unit are separated in the nth-dimension column and detected is performed repeatedly , the multi-dimensional chromatograph system further comprising:a) data collection means for collecting data items obtained in sequence by the detection unit and recording the data items by adding information to the data items or by associating the ...

Data Independent Acquisition of Product Ion Spectra and Reference Spectra Library Matching

Systems and methods are disclosed for analyzing a sample using overlapping precursor isolation windows. A mass analyzer of a tandem mass spectrometer is instructed to select and fragment at least two overlapping precursor isolation windows across a precursor ion mass range of a sample using a processor. The tandem mass spectrometer includes a mass analyzer that allows overlapping precursor isolation windows across the mass range of the sample. 1. A system for analyzing a sample using overlapping precursor isolation windows , comprising:a tandem mass spectrometer that includes a mass analyzer that allows overlapping precursor isolation windows across a mass range of a sample; anda processor in communication with the tandem mass spectrometer that instructs the mass analyzer to select and fragment at least two overlapping precursor isolation windows across the precursor ion mass range of the sample.2. The system of claim 1 , wherein the at least two overlapping precursor isolation windows are overlapped to ensure that all isotopic forms of a compound are present in at least one precursor isolation window.3. The system of claim 1 , wherein the at least two overlapping precursor isolation windows are overlapped to ensure all precursor ions across the precursor ion mass range are selected.4. The system of claim 1 , wherein each of the at least two overlapping precursor isolation windows has a width >10 amu.5. The system of claim 1 , wherein the mass analyzer allows overlapping precursor isolation windows across a mass range of a sample by moving a single precursor isolation window in a step wise manner across the mass range with precursor isolation window overlap between steps claim 1 , producing consecutive overlapping precursor isolation windows.6. The system of claim 5 , wherein the precursor isolation window overlap of the consecutive overlapping precursor isolation windows is reduced to a minimum value experimentally determined to match a fragment ion transmission ...

METHODS FOR MASS SPECTROMETRY ANALYSIS OF ENGINEERED CELL COMPOSITIONS

Provided herein are methods for generating a mass spectrometry (MS) profile of a sample from a cell composition, such as an engineered cell composition. In some embodiments, the mass spectrometry profile includes data based on one or more mass spectrometry analyses or techniques. Also provided herein are methods for, based on mass spectrometry profiles of one or more samples of such cell compositions: identifying a mass spectrometry (MS) profile of a genetically engineered cell composition comprising immune cells comprising a recombinant receptor by comparison to a reference mass spectrometry profile; characterizing a process for producing genetically engineered cell composition; assessing cell surface proteins of an engineered cell composition; and assessing a process for producing a genetically engineered cell composition. 1. A method for identifying a mass spectrometry (MS) profile of a genetically engineered cell composition , the method comprising:(a) determining a test mass spectrometry profile of a sample from a test engineered cell composition or a subset thereof using a mass spectrometry technique, said test engineered cell composition comprising immune cells comprising a recombinant receptor;(b) comparing the test mass spectrometry profile to a reference mass spectrometry profile; and(c) identifying one or more differences in the presence, absence or level of at least one data component in the test mass spectrometry profile compared to the reference mass spectrometry profile, thereby identifying a mass spectrometry profile unique to the sample.2. The method of claim 1 , wherein the reference mass spectrometry profile is based on a sample from a reference composition claim 1 , a plurality of samples from a reference composition claim 1 , or a plurality of samples from a plurality of reference compositions.3. The method of or claim 1 , wherein the test engineered cell composition is for use in an autologous cell therapy.4. The method of any of - claim 1 , ...

In vitro method for detecting avian intestinal dysbiosis

The invention pertains to an in vitro method for detecting avian intestinal dysbiosis, the method comprising determining the presence and/or level of isoleucyl-arginine (C12H25O3N5) or isomers thereof in avian sample material wherein the presence and/or an increased level of isoleucyl-arginine (C12H25O3N5) or isomers thereof in comparison to a non-affected control is indicative for avian intestinal dysbiosis.

Lipid Screening Platform Allowing a Complete Solution for Lipidomics Research

Known lipid molecules of a matrix are grouped into lipid classes and the lipid classes are further grouped into a pass-through group and a mobility separation group based on isobaric interferences. A separation system separates known lipid molecules from a matrix sample and an ion source ionizes the matrix sample. Two injections are performed. For the first injection a DMS device is put into passive mode, and for the second injection the DMS device is used to resolve isobaric interferences. A tandem mass spectrometer performs MRM scans of the pass-through group for the first injection and MRM scans of the mobility separation group for the second injection. A processor quantitates each lipid molecule in the matrix sample by comparing the MRM intensity values obtained for the first and second injections to MRM intensity and concentration values for known standards of the known lipid molecules of the matrix. 1. A system for quantitating lipids of a matrix sample using a differential mobility spectrometry (DMS) device during a targeted multiple reaction monitoring (MRM) acquisition experiment , comprising:a separation device configured to receive sequentially a first injection and a second injection of a matrix sample and to separate known lipid molecules of the matrix from the first injection and the second injection over time, wherein before the experiment the known lipid molecules of the matrix are grouped into lipid classes and the lipid classes are further grouped into a pass-through group that includes lipid classes with lipid molecules known to produce isobaric interferences with other lipid molecules and a mobility separation group that includes lipid classes with lipid molecules known to produce isobaric interferences;an ion source configured to receive separated lipid molecules from the separation device for the first injection and the second injection and to ionize the separated lipid molecules for the first injection and the second injection;a DMS device ...

LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY METHODS FOR THE ANALYSIS OF POLAR MOLECULES

A mixed-mode chromatography method for the determination of phosphorylated sugars in a sample is provided. The mixed-mode chromatography method includes obtaining a sample comprising at least one phosphorylated sugar. The sample is introduced onto a chromatography system. The chromatography system includes a column having a stationary phase material contained inside the column. The stationary phase material has a surface comprising a hydrophobic surface group and at least one ionizable modifier. The sample with a mobile phase eluent is flowed through the column, where the at least one phosphorylated sugar is substantially resolved and retained within seven minutes. The mobile phase eluent includes water with an additive and acetonitrile with the additive. The mobile phase eluent has a pH less than 6. The at least one phosphorylated sugar is detected using a detector. 1. A mixed-mode chromatography method for the determination of phosphorylated sugars in a sample , the mixed-mode chromatography method comprising:obtaining a sample comprising at least one phosphorylated sugar;introducing the sample onto a chromatography system comprising a column having a stationary phase material contained inside the column, the stationary phase material having a surface comprising a hydrophobic surface group and at least one ionizable modifier;flowing the sample with a mobile phase eluent through the column, wherein the at least one phosphorylated sugar is substantially resolved and retained within seven minutes, the mobile phase eluent comprising water with an additive and acetonitrile with the additive, the mobile phase eluent having a pH less than 6; anddetecting the at least one phosphorylated sugar using a detector.2. The mixed-mode chromatography method of claim 1 , wherein the pH of the mobile phase eluent is less than 3.3. (canceled)4. The mixed-mode chromatography method of claim 3 , wherein the pH of the mobile phase eluent is about 2.7.5. The mixed-mode chromatography ...

Immune Profiling Of Tumor Tissue

SRM/MRM assays are used to detect and quantitate proteins involved in the process of initiating, inhibiting, maintaining, and/or otherwise modulating a tumor immune response directly in patient tumor tissue. The assays provide an immune profile of the tissue microenvironment, and may be used as part of improved methods of immune-based treatment using agents that manipulate the cancer immune response together with cancer therapeutic agents. 1. A method of determining a protein expression profile in a biological sample of formalin fixed tumor tissue obtained from a cancer patient , the method comprisingdetecting and quantifying an amount of one or more fragment peptides in a protein digest prepared from said biological sample using mass spectrometry; andcalculating the amount of one or more proteins corresponding to the one or more fragment peptides in said biological sample;andwherein said one or more proteins are selected from the group consisting of B7-1, B7H2, beta-catenin, CALR, CCR4, CD133, CD137, CD137L, CD166, CD28, CD38, CD3G, CD40, CD40L, CD47, CD68, CD70, CD73, CD8A, CEACAM5, cMYC, COX-2, CXCR4, CXCR7, DNMT1, EZH2, GBP2, HMGB1, INFGR2, IL13RA2, IRF1, MyD88, NAMPT, NAPRT1, NYESO1, OX40L, PD-1, STAT3, Beclin-1, PHD2, PI3Kbeta, PI3Kdelta, PI3Kgamma, CEACAM1, IFNγ, STK11, BTK, ARG1, TDO, TGFβ1, CD16, OX40, IL-2, SLFN11, CD39, CD44, CSFIR, GZMB, PRF1, CD206, GNLY, CD3Z, ATF3, CD19, and CTLA4.2. The method of claim 1 , further comprising the step of fractionating said protein digest prior to detecting and/or quantifying the amount of said one or more fragment peptides.3. The method of claim 2 , wherein said fractionating step is selected from the group comprising gel electrophoresis claim 2 , liquid chromatography claim 2 , capillary electrophoresis claim 2 , nano-reverse phase liquid chromatography claim 2 , high performance liquid chromatography and reverse phase high performance liquid chromatography.4. (canceled)5. The method of claim 1 , wherein said protein ...

Method for evaluating mass spectrometry device, method for calibrating mass spectrometry device, analysis method, mass spectrometry device, and mass spectrometry reagent

A method for evaluating a mass spectrometry device includes: by a mass spectrometry device, performing mass spectrometry of an ester of phthalic acid and detecting a plurality of types of ions produced by dissociation of the ester of phthalic acid; and obtaining information concerning whether the mass spectrometry device is in a state suitable for analysis, based on a ratio of intensities of the plurality of types of ions detected.

Determination and Correction of Retention Time and Mass/Charge Shifts in LC-MS Experiments

Methods are described for the automatic determination and correction of retention time shift of a MS data set relative to a control data set, to correct for retention time drifts endemic to targeted LCMS analyses. In an embodiment, a 2D grid of periodic MS spectra versus time is collected for a control experiment, and RT windows are determined with an additional set of unscheduled mass spectral analyses. During successive experiments, spectra from periodic MS scans are used to determine the correspondence between the current time and the time in the control experiment. The active set of MSn scans to be acquired by the instrument is then determined as the scans with adjusted retention time windows that bracket the corrected retention time. 1. A method for acquiring Liquid Chromatography Mass Spectrometry (LC-MS) data for a plurality of analytes within a sample , the method comprising:performing a control LC-MS analysis of a plurality of analytes within a control sample, thereby generating control data;determining chromatographic retention times of one or more of the plurality of analytes within the control sample based on the control data;{'sub': RT', 'm/z, 'choosing a chunk size of the control data, the chunk size comprising a range, Δ, of retention times and a range, of Δof mass-to-charge values;'}choosing a chunk of the control data (control chunk) comprising the chunk size;storing a set of data that includes the at least one control chunk;scheduling tentative retention time windows for the plurality of analytes within the sample based on the control data, each tentative retention time window comprising a time during which at least one signal that corresponds to an analyte is to be measured, each retention time window comprising a respective start time and a respective stop time;{'sub': 'RT', 'performing at least a portion of an LC-MS analysis of the sample, thereby generating a sample chunk of LC-MS data, the sample chunk comprising a range of retention times ...

User interface for ion mobility separation device

A method of controlling the operation of an ion mobility separation device is disclosed. The method comprises displaying to a user via a user interface a pool of modes of operation of the ion mobility separation device, wherein each one of the modes is selectable by the user for inclusion in an experiment, and the modes are displayed in a first area 202 of the user interface. The method comprises receiving, via the user interface, an indication from the user of a selection of one or more instance of each one of a plurality of the modes from the pool to be included in an experiment, and an indication from the user of a set of one or more parameters for controlling the ion mobility separation device in respect of one or more selected instances of a mode. The selected instances of modes are displayed in a sequence in a second area 204 of the user interface. The operation of the ion mobility separation device is controlled in accordance with the received indications.

IDENTIFICATION AND MONITORING OF MONOCLONAL IMMUNOGLOBULINS BY MOLECULAR MASS

Disclosure herein are methods for determining whether or not an immunoglobulin is present above the polyclonal background level in a biological sample, and methods for determining whether an immunoglobulin contains a kappa or lambda light chain. These methods are useful for screening biological samples for the presence or absence of monoclonal gammopathy, and for diagnosing and monitoring monoclonal gammopathy in a subject. 1. A method of determining whether or not an immunoglobulin is present above the polyclonal background in a sample , the method comprising:a. providing a sample comprising variable region-containing immunoglobulins;b. subjecting the sample to a mass spectrometry technique to obtain a mass spectrum of the sample; andc. determining whether or not an immunoglobulin is present above the polyclonal background level by detecting the presence or absence of an M-protein peak in the mass spectrum.2. The method of claim 1 , wherein variable region-containing immunoglobulins are selected from immunoglobulin light chains claim 1 , immunoglobulin heavy chains claim 1 , and antigen binding fragments (Fabs) of immunoglobulins claim 1 , and mixtures thereof.3. The method of claim 1 , further comprising determining the presence or absence of monoclonal gammopathy in the sample based on the presence or absence of an M-protein peak in the mass spectrum.4. A method of diagnosing monoclonal gammopathy in a subject claim 1 , the method comprising:a. subjecting a subject sample comprising variable region-containing immunoglobulins to a mass spectrometry technique to obtain a mass spectrum;b. determining whether or not an immunoglobulin of the subject is present above the polyclonal background level by detecting the presence or absence of an M-protein peak in the mass spectrum; andc. diagnosing the presence or absence of monoclonal gammopathy in the subject based on whether or not an immunoglobulin is present above the polyclonal background.5. A method of monitoring a ...

SAMPLE INJECTION DEVICE

Provided herein is a sample injection method that enables efficient injection of a trace sample solution while reducing the measurement time. A sample solution is injected into a sample loop with air layers disposed on both sides of the sample solution, and the total amount of the sample solution, including the air layers, is injected into a detector. The start and the end of data collection are determined from the detection signal intensity changes that occur upon the air layers being injected into the detector, and the velocity of the flowing liquid is increased to reduce the measurement time. A washing solution is injected after the air layer to improve the washing efficiency and reduce the washing time. 1. A sample injection method for injecting a sample into a detector , using a sample loop , a container that contains a flowing solvent , a drawing section having a drawing pump , a flow path switching section that switches between (i) a first flow path joining the flowing solvent and the sample loop and a third flow path joining the sample loop and the detector and (ii) a second flow path joining the drawing section and the sample loop , and a liquid passing section having a passing pump coupled to the flow path switching section , the method comprising:switching the flow path switching section to the second flow path, to connect the drawing section including the drawing pump to the sample loop, to disconnect the passing pump from the sample loop, and to disconnect the sample loop from the detector;drawing the sample, using the drawing section with the drawing pump, into the sample loop with air layers disposed on both sides of the sample;switching the flow path switching section to the first flow path to connect the passing pump to the sample loop and the third flow path to connect the sample loop and the detector, and to disconnect the drawing section including the drawing pump from the sample loop; andpassing the flowing solvent from the container, using the ...

COMPOSITIONS AND METHODS RELATED TO OBSTRUCTIVE SLEEP APNEA

The technology concerns methods and compositions for diagnosing obstructive sleep apnea, a common condition observed in children. In certain embodiments, there are methods and compositions relating to the use of novel biomarkers to diagnose obstructive sleep apnea. 1. A method for identifying a subject as having obstructive sleep apnea (OSA) comprising:a) using a computer and an algorithm to evaluate previously measured expression levels of one or more products of one or more genes listed in Table 1 as compared to a control or reference level in a biological sample from the subject to calculate a risk score; andb) identifying the subject as having OSA based on the risk score.2. (canceled)3. The method of claim 1 , wherein a risk score calculated from an elevated level of expression of the one or more products as compared to a control or reference level indicates that the subject is likely to have OSA.4. The method of claim 1 , wherein a risk score calculated from a lower level of expression of the one or more products as compared to a risk score calculated from a control or reference level indicates that the subject is likely to have OSA.5. The method of claim 1 , wherein the control is the level of expression of the one or more products in a control sample from a subject who is known not to have OSA.6. The method of claim 1 , wherein the expression level of the one or more products is standardized against the level of expression of a corresponding standard product in the sample.7. The method of claim 1 , wherein the one or more products are one or more proteins encoded by a gene selected from the group consisting of CD14 claim 1 , CTSB claim 1 , HPX claim 1 , DPP4 claim 1 , TTR claim 1 , DEFB1|HBD1 claim 1 , FABP3 claim 1 , CP claim 1 , and AZGP1.8. The method of claim 7 , wherein the one or more products are one or more proteins encoded by one or more genes selected from the group consisting of HPX claim 7 , DPP4 claim 7 , CP claim 7 , and AZGP1.9. The method of ...

MASS SPECTROMETER

A mass spectrometer including a memory unit storing information indicating combinations of precursor ions for CIDs in respective stages. If an MSspectrum on which CID is not performed is obtained during execution of an analysis, a precursor ion selector determines whether an ion registered as a precursor ion for the first-stage CID exists on the MSspectrum, based on the list held in the memory unit. If the ion exists, an MSanalysis in which the ion is set as a precursor ion is immediately executed. Subsequently, the precursor ion selector determines whether or not an ion registered as a precursor ion for the second-stage CID in association with the precursor ion for the first-stage CID exists on an MSspectrum. If the ion exists, an MSanalysis in which the ion is set as a precursor ion is immediately executed, so that an MSspectrum is acquired. 1. A mass spectrometer capable of an MSanalysis (whose n is any integer equal to or more than 3) involving a dissociation operation conducted in at least n−1 stages , the mass spectrometer having an automatic MSanalysis function of executing , given an MS(whose m is an integer) spectrum obtained through an MSanalysis , an operation of: selecting an ion that satisfy a predetermined condition as a precursor ion for an MSanalysis from the MSspectrum; and dissociating the precursor ion and performing a mass analysis , until a value of m becomes n−1 in order from 1 , the mass spectrometer comprising:{'sup': th', 'm+1, 'a) a precursor ion information memory unit for holding information on mass-to-charge ratios of precursor ions to be dissociated in first to mstages for the MSanalysis, in association with one another; and'}{'sup': n', 'n', '1', '2', '2', '2', '3, 'b) an analysis controller configured to acquire an MSspectrum by executing, up to the MSanalysis, an operation of: determining whether or not an ion that are held as a precursor ion to be dissociated in the first stage in the precursor ion information memory unit exist on ...

6-OXO-PIPECOLIC ACID QUANTITATION BY MASS SPECTROMETRY

Methods for determining the presence or amount of oxopiperidine in a biological sample using mass spectrometry. These methods may be used to efficiently and non-invasively diagnose pyridoxine dependent epilepsy (PDE) due to deficient a-aminoadipic-δ-semialdehyde (α-AASA) dehydrogenase activity due to mutations in ALDH7A1, resulting in the accumulation of Δ-P6C, P6CH, and 6-Oxo-PIP in biological samples. 151-. (canceled)52. A method of screening for pyridoxine dependent epilepsy (PDE) in a subject , the method comprising:collecting a sample from the subject, wherein the sample is stable at room temperature for up to four months;adding deuterated 6-oxopipecolic acid (Oxo-PIP) as an internal standard to the sample;detecting whether Oxo-PIP is present in the sample by mass spectrometry; andquantifying the amount of Oxo-PIP in the sample if Oxo-PIP is present in the sample,wherein the subject is identified as having PDE when the amount of Oxo-PIP in the sample is greater than a threshold value.53. The method of claim 52 , wherein at least about 80% of Oxo-PIP in the sample remains after two weeks.54. The method of claim 52 , wherein at least about 55% of Oxo-PIP in the sample remains after four months.55. The method of claim 52 , wherein the subject is a newborn human.56. The method of claim 52 , wherein the sample is a biological fluid selected from saliva claim 52 , sweat claim 52 , urine claim 52 , blood claim 52 , serum claim 52 , plasma claim 52 , cerebrospinal fluid (CSF) claim 52 , and combinations thereof.57. The method of claim 52 , wherein the sample is collected on filter paper claim 52 , dried claim 52 , and shipped at room temperature to a facility for mass spectrometry analysis.58. The method of claim 52 , wherein the mass spectrometry is liquid chromatography tandem mass spectrometry (LC/MS-MS).59. The method of claim 58 , wherein the transitions for Oxo-PIP in mass spectra from LC/MS-MS are at 144.2 to 98.1.60. A method of diagnosing and treating ...

CHROMATOGRAPH MASS SPECTROMETRIC DATA PROCESSING METHOD AND PROCESSING DEVICE

A compound-weight time-series data calculator creates a compound spectrum matrix based on standard mass spectra of various compounds stored in a standard mass spectrum library. Then, the calculator determines, in the form of a linear regression model, the relationship of the matrix, a measured vector based on the data acquired at one measurement time point, and a compound weight vector at the measurement time point, and estimates the unknown weight vector by a minimum norm estimation in which a regularizer is introduced. A compound-weight time-series graph creator creates a compound-weight time-series graph showing a temporal change in weight for each target compound, based on the compound weight vector obtained at the measurement time points within a specified time range. A peak which appears on this graph is used for the quantitative determination of the compound or determination on the presence or absence of the compound. 2. The chromatograph mass spectrometric data processing method according to claim 1 , wherein the regularizer is an L1 norm.3. The chromatograph mass spectrometric data processing method according to claim 1 , wherein the regularizer is an L2 norm.4. The chromatograph mass spectrometric data processing method according to claim 1 , wherein an L1 norm and an L2 norm are used in a switchable manner as the regularizer claim 1 , or both the L1 norm and the L2 norm are simultaneously used as the regularizer.5. The chromatograph mass spectrometric data processing method according to claim 4 , wherein an elastic net is introduced to use the L1 norm and the L2 norm in a switchable manner or simultaneously use both the L1 norm and the L2 norm.6. A chromatograph mass spectrometric data processing device for processing mass spectrum data repeatedly acquired with a passage of time by chromatograph mass spectrometry claim 4 , comprising:a) a compound weight vector calculator for performing a maximum likelihood estimation for each of the mass spectrum data ...

Chromatographic analysis with low pressure dual gradient refocusing

There is provided a system for separation of analytes in a solution. The system encompasses a cartridge or trapping column enclosing a sorbent for binding the analytes in the solution and a conduit establishing a fluid link to a valve having a holding-loop to achieve elution through the cartridge at low pressures. Prior to entry into the loop, the eluent is diluted or modified by a confluent flow stream. The valve is switchable to a position following the elution from the cartridge for emptying the holding loop through an outlet port at high pressures comparable to those required for chromatographic columns. The system may use parallel gradient formation/elution to stagger analyses so that essentially the only analytical phase that hinders a 100% duty cycle is the time required for moving the first analyte from the valve and to the detector.

MASS-DIRECTED SEPARATION

The present invention is a method for automated mass-directed separation of two or more components from a sample, which method comprises defining a solvent gradient by its changing composition; subjecting said solvent gradient to mass spectrometry (MS) to generate gradient signal(s); passing a gradient including at least part(s) of the defined gradient across a packed chromatography column to which a sample has been applied; subjecting the eluent exiting said column to MS to generate sample signal(s); generating a spectrum by subtracting the gradient signals from the sample signals across a selected range of m/z values; and directing a fraction collector to collect fraction(s) each comprising a separated component based on the spectrum generated. 1. A method for automated mass-directed separation of two or more components of a sample by flash chromatography , which method comprisesa) defining a solvent gradient by its changing composition;{'sub': 1', '2', '3, 'b) determining a solvent noise level by subjecting said solvent gradient to mass spectrometry (MS) and generating a plurality of gradient signals t, t, tetc. across a predetermined range of m/z values;'}c) separating two or more components of a sample by passing a solvent gradient which includes at least a part of the gradient defined according to step a) across a packed flash chromatography column to which the sample has been applied;{'sub': 1', '2', '3, 'd) subjecting the eluent exiting said column to MS and generating a plurality of sample signals t′, t′, t′etc. across the predetermined range of m/z values;'}e) generating a spectrum based on the MS signals obtained in step b) and step d);f) directing a fraction collector to collect fraction(s) each comprising a separated component based on the spectrum generated in step e);{'sub': 1', '2', '3', '1', '2', '3, 'wherein in step e), gradient signals t, t, tetc. are subtracted from sample signals t′, t′, t′etc. and resulting signals are used to generate a ...

QUANTITATIVE DETERMINATION OF NUCLEOSIDE ANALOGUE DRUGS IN GENOMIC DNA OR RNA

This application provides methods to quantitate drug incorporation into DNA and of simultaneously measuring DNA methylation levels. Drugs include nucleoside analog DNA methyltransferase inhibitors. 1. A method of determining the amount of an agent incorporated in a nucleic acid following exposure to a drug comprising the following steps:(a) obtaining a biological material following exposure to a drug with a nucleic acid incorporating an agent;(b) extracting the nucleic acid from the biological material;(c) digesting the nucleic acid forming a first sample comprising dephosphorylated nucleotides;(d) adding a stable heavy-isotope labeled internal standard to the first sample to form a second sample comprising an analyte;(e) separating the analyte in the second sample using high pressure liquid chromatography;(f) adding the analyte to a mass spectrometer; and(g) quantifying the amount of the analyte in the nucleic acid to determine the amount of agent in the nucleic acid.2. The method of wherein the agent is selected from the group consisting of 5-aza-cytidine (5AC) claim 1 , 5-aza-2′-deoxycytidine (DAC) or a combination thereof.3. The method of wherein the drug is a nucleoside analog DNA methyltransferase inhibitor.4. The method of wherein the nucleoside analog DNA methyltransferase inhibitor is selected from the group comprising decitabine claim 3 , azacitidine claim 3 , guadecitabine or a combination thereof.5. The method of wherein quantifying the amount of the analyte is performed using a standard curve.6. The method of wherein the amount of agent corresponds to the amount of the analyte being normalized to the amount of a natural DNA nucleoside in the nucleic acid.7. The method of claim 1 , wherein the analyte is selected from the group consisting of 5-aza-2′-deoxycytidine (DAC) claim 1 , 5-methyl-2′-deoxycytidine claim 1 , 2′-deoxycytidine claim 1 , or a combination thereof.8. The method of claim 7 , further comprising quantifying DNA methylation by quantifying ...

OPTIMISED TARGETED ANALYSIS

A method of mass spectrometry is disclosed comprising: a) providing temporally separated precursor ions; b) mass analyzing separated precursor ions, and/or product ions derived therefrom, during a plurality of sequential acquisition periods, wherein the value of an operational parameter of the spectrometer is varied during the different acquisition periods; c) storing the spectral data obtained in each acquisition period along with its respective value of the operational parameter; d) interrogating the stored spectral data and determining which of the spectral data for a precursor ion or product ions meets a predetermined criterion, and determining the value of the operational parameter that provides this mass spectral data as a target operational parameter value; and e) mass analyzing again the precursor or product ions whilst the operational parameter is set to the target operational parameter value. 1. A method of mass spectrometry comprising:a) chromatographically separating compounds in an analytical sample and ionising the eluting sample and/or separating precursor ions, so as to provide temporally separated precursor ions;b) mass analyzing each of the separated precursor ions, and/or product ions derived therefrom, with a time of flight mass analyser during a plurality of sequential acquisition periods so as to obtain mass spectral data, wherein the value of one or more operational parameter of the spectrometer is varied such that it has different values during the different acquisition periods, and wherein the spectral data obtained for a given ion varies depending on the value of said operational parameter;c) storing the spectral data obtained in each acquisition period along with its respective value of said one or more operational parameter used in obtaining the data;d) interrogating the stored spectral data for at least one of the precursor ions, or the product ions derived therefrom, and determining which of the spectral data for that precursor ion or ...

CHROMATOGRAPHY MASS SPECTROMETRY AND CHROMATOGRAPHY MASS SPECTROMETER

Provided is a chromatography mass spectrometry capable of peak detection that can deal with a wide concentration range of a sample component and providing an evaluated value for the result. A plurality of samples having different known concentrations of a component are measured to detect a start point, an apex, and an end point of a peak. Regarding the start point, the apex, and the end point of the detected peak, an evaluated value such as probability is provided as a score to determine a score function. A component having an unknown concentration is measured to detect a start point, an apex, and an end point of a peak. Regarding the start point, the apex, and the end point of the detected peak, the score function is applied to evaluate peak detection results, and a result having a high evaluated value is selected as a peak. 1. A chromatography mass spectrometer that separates a target component of a sample for mass spectrometry , the chromatography mass spectrometer comprising a data processing unit that calculates a score function representing tendencies of a start point and an end point of a baseline and an apex of a peak with respect to a detection time at which a sample having a known component concentration is detected and a measured value of an area or a height of the component concentration , calculates a score value for a detection time at which a sample having an unknown component concentration is detected and a measured value of an area or a height of the component concentration using the calculated score function , and selects a peak of the sample having the unknown component concentration based on the calculated score value.2. The chromatography mass spectrometer according to claim 1 ,wherein the score function is a function based on frequency information that is obtained from peak detection results derived from samples having different component concentrations.3. The chromatography mass spectrometer according to claim 1 ,wherein the score function is ...

METHODS AND COMPOSITIONS CONCERNING INTESTINAL PERMEABILITY

Methods, assays and compositions for measuring intestinal permeability in subjects are provided. The methods and assays comprise the measurement of the level of food dyes, such as FD&C Blue No. 1, in blood samples shortly after the ingestion of the compositions. The methods disclosed herein are simple, cost-effective, reproducible and sensitive. 1. A method for evaluating the integrity of a subject's intestinal barrier comprising:a) administering to the subject's a pharmaceutical composition comprising disodium;2-[[4-[ethyl-[(3-sulfonatophenyl)methyl]amino]phenylH4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]cyclohexa-2,5-dien-1-ylidene]methyl]benzenesulfonate (“Blue #1”);b) assaying or measuring Blue #1 in a blood sample collected from the patient within 24 hours after the patient has been administered the oral pharmaceutical composition; andc) evaluating the integrity of the patient's intestinal barrier based on the amount of Blue #1 measured in the blood sample.2. The method of claim 1 , wherein oral pharmaceutical composition is a liquid composition.3. The method of claim 2 , wherein the volume of the pharmaceutical composition is between about 1 ml and about 500 ml.4. The method of claim 1 , wherein the subject is administered about 0.1 mg/g to 1 mg/kg of Blue #1 in step a).5. The method of claim 4 , wherein the subject is administered about 0.5 mg/kg of Blue #1 in step a).6. The method of claim 1 , wherein the pharmaceutical composition is administered to the patient orally or nasogastrically.7. The method of claim 1 , wherein measuring Blue #1 is done using mass spectrometry claim 1 , HPLC claim 1 , light spectroscopy claim 1 , or any combination thereof.8. The method of claim 1 , wherein the blood sample is collected from the subject 1 to 8 hours after the subject has been administered the pharmaceutical composition comprising Blue #1.9. The method of claim 1 , wherein the assaying is done from multiple samples collected from the subject at different ...

PESTICIDE RESIDUE DETECTION DATA PLATFORM BASED ON HIGH RESOLUTION MASS SPECTRUM, INTERNET AND DATA SCIENCE, AND METHOD FOR AUTOMATICALLY GENERATING DETECTION REPORT

Disclosed is a pesticide residue detection data platform based on high resolution mass spectrum, the Internet and data science, and a method for automatically generating a detection report. The platform includes allied laboratories, a detection result database of the allied laboratories, four basic sub-databases, a data collection system and an intelligent data analysis system. The intelligent analysis system reads data according to conditions set by a user, performs various statistical analyses according to a statistical analysis model, generates charts, obtains a comprehensive conclusion, and returns an analysis result to the client ends of the allied laboratories. 1. A pesticide residue detection data platform based on high-resolution mass spectrometry , Internet , and data science includes laboratory union , a union laboratory detection result database and four basic sub-databases , a data acquisition system , and an intelligent data analysis system , wherein ,the laboratory union refers to several standard laboratories established across the country, which are operated under five unified specifications in a closed system and detect pesticide residues in fruits and vegetables on the market throughout the country all year;the union laboratory detection result database contains names of pesticides, names of agricultural products, sampling times, sampling locations, detection methods, and detection organizations; the four basic sub-databases are a multi-country MRL(maximum residue limit) database, an agricultural product category database, a pesticide information database, and a geographic information database;the data acquisition system realizes automatic uploading of detection result, data preprocessing, and contamination level judgment, to establish a national pesticide residue detection result database;the data acquisition system comprises a data acquisition module, a data preprocessing module, a contamination level judgment module, and a data storage module; ...

QUANTIFICATION OF TRANSTHYRETIN AND ITS ISOFORMS

The present invention relates to assays and methods for the detection of transthyretin and its isoforms. Specifically, the assays and methods of the present invention embrace liquid chromatography and mass spectrometry. The present invention also relates to unique peptides and peptide variants useful in the assays and methods. 1. A method of determining the concentration of an isoform of transthyretin in a sample comprising:(a) obtaining a sample from a subject;(b) treating said sample to digest one or more isoforms of transthyretin proteins contained therein;(c) generating a mass spectrometry profile of the digested sample of step (b);(d) comparing the mass spectrometry profile from step (c) to a standard curve, wherein said standard curve has been created using at least one calibration standard selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10, SEQ ID NO. 11, SEQ ID NO. 12, SEQ ID NO. 13, SEQ ID NO. 14, SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17 and variants thereof; and(e) calculating a concentration of said one or more isoforms of transthyretin in the sample obtained from the subject based on the standard curve.2. The method of wherein the sample of step (b) is subjected to liquid chromatography prior to the generation of said mass spectrometry profile.3. The method of claim 1 , further comprising spiking the sample of (a) with a known concentration of one or more peptides or proteins selected from the group consisting of SEQ ID NO. 1 claim 1 , SEQ ID NO. 2 claim 1 , SEQ ID NO. 3 claim 1 , SEQ ID NO. 4 claim 1 , SEQ ID NO. 5 claim 1 , SEQ ID NO. 6 claim 1 , SEQ ID NO. 7 claim 1 , SEQ ID NO. 8 claim 1 , SEQ ID NO. 9 claim 1 , SEQ ID NO. 10 claim 1 , SEQ ID NO. 11 claim 1 , SEQ ID NO. 12 claim 1 , SEQ ID NO. 13 claim 1 , SEQ ID NO. 14 claim 1 , SEQ ID NO. 15 claim 1 , SEQ ID NO. 16 claim 1 , SEQ ID NO. 17 claim 1 , SEQ ID NO. 18 claim 1 , SEQ ID NO. 19 claim 1 , SEQ ID NO. 20 claim 1 , SEQ ID ...

CHIRAL ANALYSIS METHOD OF BOUND AMINO ACID AND CHIRAL ANALYSIS SYSTEM

A chiral analysis method of a bound amino acid includes a step of hydrolyzing a bound amino acid using a deuterium chloride-deuterium oxide solution and/or deuterium oxide; a step of separating, by chiral separation, a D-form and an L-form of an amino acid generated by the hydrolyzation; a step of generating fragments from the separated amino acid; and a step of selecting and analyzing a predetermined fragment that contains an α carbon and does not contain a side chain from the generated fragments, by mass spectrometry. 1. A chiral analysis method of a bound amino acid comprising:a step of hydrolyzing a bound amino acid using a deuterium chloride-deuterium oxide solution and/or deuterium oxide;a step of separating, by chiral separation, a D-form and an L-form of an amino acid generated by the hydrolyzation;a step of generating fragments from the separated amino acid; anda step of selecting and analyzing a predetermined fragment that contains an α carbon and does not contain a side chain from the generated fragments, by mass spectrometry.2. The chiral analysis method of the bound amino acid according to claim 1 , wherein the D-form and the L-form of the amino acid generated by the hydrolyzation are separated by the chiral separation through a chromatographic method.3. The chiral analysis method of the bound amino acid according to claim 1 , further comprising:a step of derivatizing the amino acid generated by the hydrolyzation,wherein the D-form and the L-form of the derivatized amino acid are separated by the chiral separation.4. The chiral analysis method of the bound amino acid according to claim 1 ,wherein in the step of generating the fragments, the fragments are generated for each of the separated D-form and the L-form of the amino acid, andwherein in the step of analyzing, the predetermined fragment that contains the α carbon and does not contain the side chain is selected for each of the separated D-form and the L-form of the amino acid, and an abundance ...

Systems, devices, and methods for generating machine learning models and using the machine learning models for early prediction and prevention of preeclampsia

Disclosed herein are methods and systems for determining risk of preeclampsia. The system can include (a) a computer comprising: (i) a processor; and (II) a memory, coupled to the processor, the memory storing a module comprising: (1) test data for a sample from a subject including values indicating a quantitative measure of one or more markers; (2) a classification rule which, based on values including the measurements, classifies the subject as being at risk of preeclampsia, wherein the classification rule is configured to have a sensitivity of at least 75%, at least 85% or at least 95%; and (3) computer executable instructions for implementing the classification rule on the test data.

PROCESS FOR THE PREPARATION OF ARIPIPRAZOLE LAUROXIL

It is provided a process for the preparation of aripiprazole lauroxil that comprises reacting 1-(hydroxymethyl) aripiprazole with lauric acid in the presence of a suitable solvent and a carboxyl activating agent in the presence of a suitable solvent and, optionally, in the presence of an appropriate base. 1-(Hydroxymethyl) aripiprazole can be prepared by reacting aripiprazol or an hydrate thereof with paraformaldehyde in the presence of a suitable organic solvent and a suitable base, wherein the reaction is carried out without the addition of water as a solvent to the reaction mixture. Additionally, (7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-3,4-dihydro-2-oxoquinolin-1(2H)-yl)methyl formate is provided as a reference standard.

TRIMETHYLAMINE-CONTAINING COMPOUNDS FOR DIAGNOSIS AND PREDICTION OF DISEASE

The present invention provides markers and methods for determining whether a subject, particularly a human subject, has or is at risk of developing, a disease such as cardiovascular disease, diabetes mellitus, insulin resistance, metabolic syndrome, NAFLD (Nonalcoholic Fatty Liver Disease) or NASH (Nonalcoholic Steatohepatitis) (e.g., within the ensuing year, two years, and/or three years). The present application also relates to the use of such markers and methods for monitoring the status of such diseases in a subject or the effects of therapeutic agents on subjects with such diseases. 1. A method of identifying a subject having or at risk of cardiovascular disease or at risk of a complication of cardiovascular disease , comprising:a) determining levels of a trimethylamine (TMA)-containing compound in a biological sample obtained from the subject, wherein the TMA-containing compound is selected from crotonobetaine, gamma-butyrobetaine, or carnitine; andb) comparing levels of said TMA-containing compound in said biological sample to a control value;wherein a subject whose levels of said TMA-containing compound in said biological sample are elevated as compared to said control value has or is at risk for developing cardiovascular disease or a complication of cardiovascular disease.2. The method of claim 1 , further comprising step c) treating said subject with a therapeutic that reduces the symptoms of cardiovascular disease or that reduces the risk of cardiovascular disease.3. The method of claim 2 , wherein said therapeutic is selected from the group consisting of: an antibiotic claim 2 , a probiotic claim 2 , an alpha-adrenergic blocking drug claim 2 , an angiotensin-converting enzyme inhibitor claim 2 , an antiarrhythmic drug claim 2 , an anticoagulant claim 2 , an antiplatelet drug claim 2 , a thromybolytic drug claim 2 , a beta-adrenergic blocking drug claim 2 , a calcium channel blocker claim 2 , a brain acting drug claim 2 , a cholesterol-lowering drug claim ...

POROUS CYCLODEXTRIN POLYMERIC MATERIALS AND METHODS OF MAKING AND USING SAME

A nucleophilic substitution reaction to crosslink cyclodextrin (CD) polymer with rigid aromatic groups, providing a high surface area, mesoporous CD-containing polymers (P-CDPs). The P-CDPs can be used for removing organic contaminants from water. By encapsulating pollutants to form well-defined host-guest complexes with complementary selectivities to activated carbon (AC) sorbents. The P-CDPs can rapidly sequester pharmaceuticals, pesticides, and other organic micropollutants, achieving equilibrium binding capacity in seconds with adsorption rate constants 15-200 times greater than ACs and nonporous CD sorbents. The CD polymer can be regenerated several times, through a room temperature washing procedure, with no loss in performance. 5. The mesoporous polymeric material of claim 2 , wherein the molar ratio of cyclodextrin moieties to aryl moieties ranges from about 1:1 to about 1:X claim 2 , wherein X is three times the average number of glucose subunits in the cyclodextrin moieties.6. The mesoporous polymeric material of claim 2 , wherein the cyclodextrin is selected from the group consisting of α- claim 2 , β- claim 2 , γ-cyclodextrin claim 2 , and combinations thereof.7. The mesoporous polymeric material of claim 2 , wherein the cyclodextrin moieties comprise β-cyclodextrin.8. The mesoporous polymeric material of claim 7 , wherein the cyclodextrin moieties comprise β-cyclodextrin and the ratio of β-cyclodextrin moieties to crosslinking moieties is 1:1 to 1:21.9. The mesoporous polymeric material of claim 2 , wherein the mesoporous polymeric material has a Brunauer-Emmett-Teller (BET) surface area of 50 m/g to 2000 m/g.10. The mesoporous polymeric material of claim 3 , wherein the molar ratio of cyclodextrin moieties to aryl moieties ranges from about 1:1 to about 1:X claim 3 , wherein X is three times the average number of glucose subunits in the cyclodextrin moieties.11. The mesoporous polymeric material of claim 3 , wherein the cyclodextrin is selected from ...

METHODS FOR ASSESSING BINDING AFFINITY OF AN ANTIBODY VARIANT TO THE NEONATAL FC RECEPTOR

The present invention provides methods to quickly and efficiently assess the effect of antibody variants, including PTMs, e.g., glycosylation, oxidation, and deamidation variants, on the binding between the antibody and FcRn. In particular, the present invention is based, at least in part, on the development of an online, two dimension liquid chromatography (2D-LC) method for assessing binding between antibody variants and FcRn. In one aspect, the online 2D-LC is coupled with mass spectrometry (MS). The present invention allows for differentiation of antibody variants by peak pattern and retention time profile by affinity chromatography, and identification of these variants by mass spectrometry analysis. 1. A method for assessing binding affinity of an antibody variant to the neonatal Fc receptor (FcRn) , or a fragment thereof , using an online two dimension liquid chromatography system , the method comprising:a) contacting a first sample comprising antibody variants to an affinity chromatography stationary phase at an acidic pH, wherein the affinity chromatography stationary phase comprises immobilized FcRn or a fragment thereof, to thereby bind the antibody variants to the stationary phase;b) eluting the first sample from the affinity chromatography stationary phase using a positive pH gradient, to obtain an eluted sample;c) contacting the eluted sample to a reverse phase chromatography stationary phase; andd) eluting the reverse phase chromatography in a mobile phase to obtain a second eluted sample,wherein antibody variants that elute ahead of a control sample are identified as having weaker binding affinity to FcRn than the control sample.2. The method of claim 1 , further comprising analyzing the second eluted sample using mass spectrometry (MS).3. The method of claim 1 , wherein the acidic pH is a pH of about 6.0 or less.4. The method of claim 1 , wherein the positive pH gradient comprises an increase in pH from about pH 6.0 to about pH 8.8.5. The method of ...

METHOD FOR DIAGNOSING STOMACH CANCER USING CHANGE OF TRYPTOPHAN METABOLISM

The present disclosure relates to stomach cancer diagnosis using tryptophan metabolism rate in one aspect, and it relates to an invention using change of tryptophan metabolism rate in a stomach cancer patient, which is different from a normal person. 1. A method for diagnosing stomach cancer , comprising:measuring concentrations of tryptophan, anthranilic acid, serotonin, kynurenine, indole sulfate, nicotinic acid and nicotinamide in blood collected from an evaluation subject; anddiagnosing to have stomach cancer possibility in the case that blood concentration of at least one selected from the group consisting of tryptophan, anthranilic acid, serotonin, kynurenine and indole sulfate is lower than that of blood concentration of a normal person, or in the case that blood concentration of at least one selected from the group consisting of nicotinic acid and nicotinamide is higher than that of blood concentration of a normal person.2. The method for diagnosing stomach cancer according to claim 1 , wherein the diagnosing is to diagnose to have stomach cancer possibility in at least one case selected from the group consisting of: decreasing of blood concentration ratio of anthranilic acid/tryptophan claim 1 , decreasing of blood concentration ratio of serotonin/tryptophan claim 1 , increasing of blood concentration ratio of kynurenine/tryptophan claim 1 , increasing of blood concentration ratio of nicotinic acid/tryptophan and increasing of blood concentration ratio of nicotinamide/tryptophan claim 1 , compared to a normal person.3. The method for diagnosing stomach cancer according to claim 1 , wherein the diagnosing is to diagnose to have stomach cancer possibility in at least one case selected from the group consisting of: concentration ratio of anthranilic acid/tryptophan of 0.0005 to 0.003 claim 1 , concentration ratio of serotonin/tryptophan of 0.003 to 0.006 claim 1 , concentration ratio of kynurenine/tryptophan of 0.01 to 0.04 claim 1 , concentration ratio of ...

METHOD AND APPARATUS FOR THE EQUILIBRATION OF A PACKED CHROMATOGRAPHY COLUMN

Disclosed is a method for equilibrating a chromatography column including the steps of (i) providing a mobile phase; and (ii) passing the mobile phase through a packed chromatography column; wherein the mobile phase includes two liquids, the proportions of which change as it is passed through the column. Also discussed are automated aspects of the method, as well as a system capable of performing such method. 113-. (canceled)14. A method for equilibrating a chromatography column including the steps of (i) providing a packed chromatography column; and (ii) passing a pressurized mobile phase through said column; wherein the mobile phase is obtained by combining at least two liquids , the proportions of which are varied as the mobile phase is passed through the column.15. A method according to claim 14 , wherein the variation of said at least two liquids is achieved by combining an increasing proportion of one liquid and a decreasing proportion of another liquid to provide a linear gradient in the mobile phase as it passes the column.16. A method according to claim 14 , wherein at least one of the liquids is an organic solvent.17. A method according to claim 14 , where the mobile phase is passed through the column at a flow rate in the range of 10-200 ml/min.18. A method according to claim 14 , wherein the column is packed with a media.19. A method according to claim 14 , wherein the surface area of the packing available to the mobile phase is at least 500 m/g (dry weight) or greater.20. A method according to claim 14 , wherein the column and/or the column frits are made of a polymeric material claim 14 , such as polypropylene or polyethylene.21. A method according to claim 14 , wherein the size and material of the column as well as the packing surface area available to the mobile phase are used as parameters to define an equilibration gradient comprised of two liquids claim 14 , the proportions of which are varied as the mobile phase is passed through the column claim ...

Antimicrobials from an epigenetics based fungal metabolite screening program

Novel antimicrobial compounds and associated methods of development are presented herein.

TWO-DIMENSIONAL LIQUID CHROMATOGRAPHY SYSTEM FOR HEART-CUT METHOD

Provided is a two-dimensional liquid chromatography system, and more particularly, a two-dimensional liquid chromatography system capable of performing both independent one-dimensional separation through a reversed-phase or normal-phase chromatography method and two-dimensional separation for removing a matrix effect in a single system. 1. A two-dimensional liquid chromatography system characterized in that in a reversed-phase or normal-phase two-dimensional liquid chromatography system , a first switching valve and a second switching valve are switched so that among materials separated in a first column , only a material of interest is selectively re-separated in a second column supposing that the material of interest is co-eluted with the matrix during the separation of materials in the first column , but the material of interest reaching the second column is diluted by a diluting mobile phase supplied through a second mobile-phase pump connected to the first switching valve to thereby be analyzed in a mass spectrometer (MS).2. The two-dimensional liquid chromatography system of claim 1 , wherein it comprises:the first column primarily separating materials in an injected sample;the first switching valve adjusting the materials separated in the first column so as to be introduced through a second inlet port and then discharged to the outside through a first drain port or discharged through a second outlet port and including a mobile-phase inlet port connected to the second mobile-phase pump so that the diluting mobile phase is introduced therethrough, and a mobile-phase outlet port through which the diluting mobile phase is discharged;the second switching valve adjusting the materials discharged to the second outlet port so as to be directly moved to the mass spectrometer (MS) or discharged to a third outlet port;a T shaped connector tube including a first port connected to the mobile-phase outlet port of the first switching valve, a second port connected to the ...

Method for establishing shenqi fuzheng injection fingerprint spectrum

A method for establishing a Shenqi Fuzheng injection fingerprint spectrum, comprising: employing an ultra-high voltage liquid chromatography mass spectrometer to test the Shenqi Fuzheng injection, the chromatography conditions including: chromatographic column: Agilent Zorbax Eclipse Plus C18, 2.1 mm×100 mm, 1.8 μm; mobile phase: mobile phase A is 0.1% formic acid aqueous solution, and mobile phase B is 0.1% formic acid acetonitrile solution; employing gradient elution procedure as follows: 0-0.5 min, 95% of mobile phase A, and 5% of mobile phase B; 0.5-10 min, 95%-75% of mobile phase A, and 5%-25% of mobile phase B; 10-15 min, 75%-45% of mobile phase A, and 25%-55% of mobile phase B; 15-18 min, 45%-0% of mobile phase A, and 55%-100% of mobile phase B; and 18-20 min, 0% of mobile phase A, and 100% of mobile phase B.

QUANTITATION OF TAMOXIFEN AND METABOLITES THEREOF BY MASS SPECTROMETRY

Provided are methods for determining the amount of tamoxifen and its metabolites in a sample by mass spectrometry. In some aspects, the methods provided herein determine the amount of norendoxifen. In some aspects, the methods provided herein determine the amount of norendoxifen and tamoxifen. In some aspects, the methods provided herein determine the amount of norendoxifen and other tamoxifen metabolites. In some aspects, the methods provided herein determine the amount of tamoxifen, norendoxifen, and other tamoxifen metabolites. 1. A method for determining an amount of tamoxifen and N-Desmethyl Tamoxifen in a human sample in a single mass spectrometry assay , comprising:(a) purifying the sample by liquid chromatography;(b) ionizing said tamoxifen and N-Desmethyl Tamoxifen to produce one or more ions detectable by mass spectrometry; and(c) detecting an amount of the ion(s) from step (b) by mass spectrometry; wherein the amount of the ion(s) detected is related to the amount of each of tamoxifen and N-Desmethyl Tamoxifen in said sample,wherein the method has a limit of quantitation of less than or equal to 1.5 ng/mL for tamoxifen and N-Desmethyl Tamoxifen.2. The method of claim 1 , further comprising protein precipitation prior to step (a).3. The method of claim 1 , further comprising filtration prior to step (a).4. The method of claim 1 , wherein said liquid chromatography is high pressure liquid chromatography (HPLC).5. The method of claim 1 , wherein said liquid chromatography is high turbulence liquid chromatography (HTLC).6. The method of claim 1 , further comprising detecting the amount of an internal standard.7. The method of claim 1 , wherein said ionization is in positive ion mode.8. The method of claim 1 , wherein said sample is a serum or plasma sample.9. The method of claim 1 , wherein said mass spectrometry is tandem mass spectrometry.10. The method of claim 1 , wherein further comprising determining an amount of metabolites selected from the group ...

Rapid Method of Forensic Toxicology in Post-Mortem Individuals Using Muscle Tissue Testing

The present invention provides a rapid method for forensic drug testing in a post-mortem individual using muscle tissue and fluid associated with the muscle tissue obtained from remains of the post-mortem individual. The method comprises obtaining muscle tissue and associated fluid from a post-mortem individual, collecting the fluid associated with the muscle tissue, analyzing the fluid associated with the muscle tissue to detect and quantify one or more non-naturally occurring drugs in the post-mortem individual, and identifying the one or more non-naturally occurring drugs in the post-mortem individual. The detection and quantification of non-naturally occurring drugs in muscle tissue and associated fluid is surprisingly faster than detection and quantification of the non-naturally occurring drugs in muscle tissue obtained from the same post-mortem individual and prepared as muscle tissue homogenates using the LC-MS/MS method, with results obtained in as soon as three hours. 1. A rapid method for the detection and quantification of non-naturally occurring drugs for forensic drug testing in a post-mortem individual using muscle tissue and associated fluid obtained from remains of the post-mortem individual , comprising:obtaining a sample of muscle tissue and fluid associated with the muscle tissue from remains of a post-mortem individual;collecting the muscle tissue fluid for analysis;analyzing the sample of muscle tissue fluid using Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to detect and quantify the one or more non-naturally occurring drugs in the post-mortem individual; andidentifying the one or more non-naturally occurring drugs in the post-mortem individual, wherein detection and quantification in the muscle tissue fluid is faster than detection and quantification of the non-naturally occurring drugs in muscle tissue obtained from the same post-mortem individual and prepared as muscle tissue homogenates using the LC-MS/MS method, ...

KIT FOR PREPARING SAMPLE FOR DETECTING MONOCLONAL ANTIBODY

A sample preparation kit related to the present invention provides a significantly versatile analytical technique that is not affected by the diversity of antibodies, difference in species, matrix and the like. For preparing a sample to be used for detection of a monoclonal antibody through high-performance liquid chromatography-mass spectrometry (LC-MS), the kit includes a porous body for immobilizing a monoclonal antibody to be detected; nanoparticles with an immobilized protease; a reaction vessel for selectively digesting the monoclonal antibody by bringing the porous body and nanoparticles into contact; a buffer to be introduced into the reaction vessel along with the nanoparticles and porous body so that a protease reaction is carried out; and a filtration membrane to remove the porous body and nanoparticles after the proteolysis so as to extract the reaction product and the buffer. 111-. (canceled)12: A kit for preparing a sample for detection of a monoclonal antibody through high-performance liquid chromatography-mass spectrometry , comprising:a porous body that immobilizes a monoclonal antibody;nanoparticles having an immobilized protease;a reaction vessel that selectively proteolyses the monoclonal antibody by bringing the porous body and nanoparticles into contact;a buffer to be introduced into the reaction vessel along with the nanoparticles and porous body such that a protease Proteolysis reaction is carried out; anda filtration membrane that removes the porous body and nanoparticles after the Proteolysis reaction and extracts a Proteolysis reaction product and the buffer,wherein the filtration membrane functions as a bottom of the reaction vessel which hardly permeates the buffer and a peptide produced through the protease Proteolysis reaction under a condition that no pressure or centrifugal force is applied and permeates the buffer and peptide under a condition that pressure or centrifugal force is applied.13: The kit according to claim 12 , wherein ...

IDENTIFICATION OF BLOOD BASED METABOLITE BIOMARKERS OF PANCREATIC CANCER

The present disclosure relates to a panel of a plurality of metabolite species that is useful for the identification or detection of subjects having pancreatic cancer, including methods for identifying such metabolic biomarkers within biological samples. The disclosure also includes a statistical model for predicting the presence of pancreatic cancer in a subject's biofluid by quantifying and comparing positive and negative fold changes in metabolite species' concentration; comparing the subject's metabolite species' concentrations to a predetermined value. 1. A method comprising:measuring the concentration of at least two metabolite species in a sample of a biofluid from a subject to be tested for pancreatic cancer, wherein the at least two metabolite species is a component of a panel of a plurality of metabolite species,wherein a change in the concentration of the metabolite species is a characteristic that is associated with pancreatic cancer.2. The method of wherein the concentration of the metabolite species is normalized.3. The method of claim 1 , further comprising the step of:comparing the measured concentration of the at least two metabolite species to a predetermined value calculated using a model based on concentrations of a plurality of the metabolite species that are components of the panel.4. The method of claim 1 , wherein the panel comprises two to nine metabolite species selected from the group consisting of alanine claim 1 , creatinine claim 1 , formate claim 1 , glucose claim 1 , glutamate claim 1 , glutamine claim 1 , histidine claim 1 , lactate claim 1 , and valine.5. The method of wherein the panel comprises metabolite species that have been identified by a plurality of methods selected from the group consisting of nuclear magnetic resonance (NMR) spectroscopy claim 1 , gas chromatography-mass spectrometry (GC-MS) claim 1 , liquid chromatography-mass spectrometry (LC-MS) claim 1 , correlation spectroscopy (COSy) claim 1 , nuclear Overhauser ...

Microbial Identification and Quantitation Using MS Cleavable Tags

Systems and methods are provided for microbial identification using cleavable tags. Control information is sent to a mass spectrometer to select a peptide labeled with a first tag of a known microbe, fragment the labeled peptide of the known microbe, and monitor for an intensity of the first tag in an MRM method using a processor. An ion source provides a beam of ions from a sample that includes peptides labeled with the first tag. The first tag binds to a peptide of a known microbe and is cleaved from the peptide of the known microbe during mass spectrometry. The mass spectrometer receives the beam of ions and is adapted to perform the MRM method on the beam of ions. If the intensity of the first tag received from the mass spectrometer exceeds a threshold value, the known microbe is identified in the sample using the processor. 1. A system for microbial identification using cleavable tags that bind to peptides , comprising:an ion source that provides a beam of ions from a sample that includes peptides labeled with a first tag that binds to a peptide of a known microbe and is cleaved from the peptide of the known microbe during mass spectrometry;a mass spectrometer that receives the beam of ions and is adapted to perform a multiple reaction monitoring (MRM) method on the beam of ions; and sends control information to the mass spectrometer to select the labeled peptide of the known microbe, fragment the labeled peptide of the known microbe, and monitor for an intensity of the first tag in the MRM method, and', 'if the intensity of the first tag received from the mass spectrometer exceeds a threshold value, identifies the known microbe in the sample., 'a processor in communication with the mass spectrometer and the ion source that'}2. The system of claim 1 , wherein the first tag includes two or more copies of a mass spectrometry enhancing group and the intensity of the first tag is an intensity of the mass spectrometry enhancing group.3. The system of claim 1 , ...

SYSTEM LAYOUT FOR AN AUTOMATED SYSTEM FOR SAMPLE PREPARATION AND ANALYSIS

A sample preparation and analysis system. The system includes a housing with a sample preparation station and a sample analysis station positioned within the housing. The sample analysis station is spaced away from the sample preparation station. A transport assembly is configured to move at least one sample within the housing and between the sample preparation station and the sample analysis station. 1. A sample preparation and analysis system , comprising:a housing;a sample preparation station positioned within the housing;a sample analysis station positioned within the housing and interconnected in an automated manner with the sample preparation station; anda transport assembly configured to move at least one sample within the housing in an automated manner between the sample preparation station and the sample analysis station.2. The sample preparation and analysis system of claim 1 , wherein the sample preparation station is positioned substantially on one side of the housing claim 1 , at a height that is greater than a height of a base of an analyzer included in the sample analysis station; andthe analyzer is positioned substantially on the other side of the housing, at a height that is less than a height of a base of the sample preparation station.3. The sample preparation and analysis system of claim 1 , the sample analysis station includes a mass spectrometer and one or more liquid chromatography pumps and at least one liquid chromatography mobile phase container claim 1 , the at least one liquid chromatography mobile phase container being positioned at a height that is greater than a height of the one or more liquid chromatography pumps.4. The sample preparation and analysis system of claim 1 , wherein the sample analysis station includes an analyzer selected from the group consisting of a liquid chromatography mass spectrometer claim 1 , a gas chromatography mass spectrometer claim 1 , a surface desorption/ionizer directly coupled to a mass spectrometer ...

Monitoring Ion Mobility Spectrometry Environment for Improved Collision Cross Section Accuracy and Precision

A mass spectrometer is disclosed comprising an ion mobility separator 4 for separating ions according to their ion mobility, one or more first devices or stages arranged upstream of the ion mobility separator and a control system. The control system is arranged and adapted to monitor directly or indirectly the operating environment within the ion mobility separator 4 , and to control the operating environment within the ion mobility separator 4 based on the monitoring by controlling one or more gas flows to or within one or more of the one or more first devices or stages.

Quantitation Throughput Enhancement by Differential Mobility Based Pre-Separation

A system for analyzing a sample includes a source configured to generate ions from constituent components of the sample; a mobility separator configured to separate ions received from the source based on the mobility in a gas; a plurality of ion channels arranged adjacent to the plurality of exit apertures of the mobility separator such that ions from the mobility separator are directed to different channels according to their respective mobility; a mass analyzer configured to determine the mass-to-charge ratio of the ions; and a controller. The controller is configured to identify retention time windows with minimum overlap of ions with similar mobility and sets of ions within the retention time windows; adjust mobility separation parameters for specific sets of ions to optimize separation of compounds; and quantify a plurality of target analytes.

VITAMIN B2 DETECTION BY MASS SPECTROMETRY

Methods are described for measuring the amount of a vitamin B2 in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying vitamin B2 in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric techniques. 1. A method for determining the amount of vitamin B2 in a biological sample from a human , said method comprising:(a) adding an internal standard to the sample;(b) subjecting the sample to liquid chromatography;(c) ionizing vitamin B2 and the internal standard under conditions suitable to produce one or more ions detectable by tandem mass spectrometry;(d) determining the amount of said one or more ions by tandem mass spectrometry; and(e) comparing the amount of said one or more ions of vitamin B2 and said one or more ions of the internal standard to determine the amount of vitamin B2 in the sample.2. The method of claim 1 , wherein said liquid chromatography and mass spectrometry are conducted with on-line processing.3. The method of claim 1 , wherein said biological sample comprises plasma or serum.4. The method of claim 1 , wherein said one or more ions detectable by mass spectrometry comprise one or more ions of vitamin B2 selected from the group consisting of ions with a mass to charge ratio of 377.2±0.5 and 243.2±0.5.5. The method of claim 1 , wherein said one or more ions detectable by mass spectrometry comprise one or more ions of the internal standard selected from the group consisting of ions with a mass to charge ratio of 380.2±0.5 and 246.2±0.5.6. The method of claim 1 , wherein the liquid chromatography is a high performance liquid chromatography (HPLC).7. The method of claim 1 , wherein the liquid chromatography is a reverse-phase high performance liquid chromatography (RP-HPLC).8. The method of claim 1 , wherein said method has a lower limit of quantitation within the range of 5 nmol/L and 25 nmol/L claim 1 , inclusive.9. The method of claim 1 , further comprising protein ...

METHODS FOR RNA ANALYSIS

The present invention is concerned with methods for analyzing RNA molecules. The provided methods involve conjugates for RNA cleavage comprising a chemical moiety with RNA cleaving activity and an oligonucleotide. The oligonucleotide is designed based on a target sequence present in an RNA molecule, and the cleavage of the RNA molecule is inter alia carried out at conditions allowing the hybridization of the oligonucleotide to the target 5 sequence. Thereby, the method is easily applicable to RNA molecules of any sequence. The method further involves the analysis of the RNA fragments obtained after cleavage to obtain information on the physical properties of the RNA molecule. 1. A method for analyzing an RNA molecule comprising the following steps:(i) providing an RNA molecule;(ii) providing at least one conjugate comprised of a chemical moiety with RNA cleaving activity and an oligonucleotide, wherein the sequence of said oligonucleotide is complementary to a target sequence of the RNA molecule;(iii) cleaving the RNA molecule provided in step (i) to obtain RNA fragments by contacting the RNA molecule with the at least one conjugate provided in step (ii) under conditions allowing the hybridization of said oligonucleotide to said target sequence and the cleavage of the RNA molecule; and(iv) determining a physical property of the RNA molecule by analyzing one or more of the RNA fragments obtained in step (iii),wherein the RNA molecule is an mRNA molecule.2. The method of claim 1 , wherein cleaving the RNA molecule results in a 5′ fragment claim 1 , a 3′ fragment and optionally one or more central fragments.3. The method of or claim 1 , wherein the fragments are separated from each other before analyzing the one or more of the RNA fragments in step (iv).4. The method of claim 3 , wherein the fragments are separated by chromatography claim 3 , preferably by HPLC or by an affinity chromatography including an oligo-dT based capturing column chromatography.5. The method of ...

ANALYSIS METHOD, ANALYSIS DEVICE AND NON-TRANSITORY COMPUTER READABLE RECORDING MEDIUM STORING

An analysis method is a method of analyzing a second substance in a sample including the second substance produced by decomposition of a first substance, and includes analyzing a sample and a compound having a known concentration and detecting the first substance, the second substance and the above-mentioned compound, calculating an intensity or a concentration of the first substance obtained from the above-mentioned data based on data obtained by the detection and a relative response factor in regard to the first substance and the above-mentioned compound, and producing information about an amount or a concentration of the second substance excluding the second substance produced from the first substance in the analysis, based on an intensity or a concentration of the first substance. 1. An analysis method of analyzing a second substance produced by decomposition of a first substance , including:analyzing a sample and a compound having a known concentration and detecting the first substance, the second substance and the compound;calculating an intensity or a concentration of the first substance based on data obtained by the detection and a relative response factor in regard to the first substance and the compound; andproducing information about an amount or a concentration of the second substance excluding the second substance produced from the first substance in the analysis, based on an intensity or a concentration of the first substance obtained from the data.2. The analysis method according to claim 1 , including acquiring a first threshold value in regard to an intensity or a concentration of the first substance claim 1 , andthe analysis method producing the information based on a concentration of the second substance obtained by the data and whether an intensity or a concentration of the first substance satisfies a first condition based on the first threshold value.3. The analysis method according to claim 2 , including acquiring a second threshold value in ...

LIQUID CHROMATOGRAPH MASS SPECTROMETER

The invention provides a liquid chromatograph mass spectrometer which prevents contamination of a pump and a column and can perform mass calibration without adding a complicated mechanism. This liquid chromatograph mass spectrometer includes a liquid chromatograph including a liquid feed pump configured to feed a mobile phase solvent, a mass spectrometer configured to analyze a mass of a sample, and a standard sample container configured to be connected in series with the liquid chromatograph and the mass spectrometer in a flow path that connects the liquid chromatograph and the mass spectrometer and configured to house a standard sample for mass calibration. 1. A liquid chromatograph mass spectrometer , comprising:a liquid chromatograph including a liquid feed pump configured to feed a mobile phase solvent;a mass spectrometer configured to analyze a mass of a sample; anda standard sample container configured to be installed in a flow path connecting the liquid chromatograph and the mass spectrometer, configured to be connected in series with the liquid chromatograph and the mass spectrometer, and configured to house a standard sample for mass calibration.2. The liquid chromatograph mass spectrometer according to claim 1 , wherein a cylindrical case that includes an injection hole at a first end and a discharge hole at a second end and that has a flow path direction as a longitudinal direction, and', 'a partition plate configured to be movable along an inner wall of the case and partitioning an inside of the case, and wherein, 'the standard sample container includesthe partition plate is configured to be movable in a direction of the discharge hole due to movement of a mobile phase solution from the injection hole.3. The liquid chromatograph mass spectrometer according to claim 1 , wherein a case that includes an injection hole at a first end and a discharge hole at a second end, and', 'a tube connected between the injection hole and the discharge hole in the case ...

METHODS OF PREPARING SAMPLES FOR PROTEOMIC ANALYSIS

Provided herein are methods of preparing a protein sample for proteomic analysis. In exemplary embodiments, the method comprises (a) contacting a blood sample comprising proteins with a protective agent comprising an anticoagulant (AC) and an aldehyde releaser (AR), to obtain a mixture, optionally, wherein the blood sample is added to a blood collection tube (BCT) comprising the protective agent, and (b) isolating a fraction comprising proteins or a source of proteins from the mixture to yield a protein sample or a source of a protein sample, wherein steps of the method are carried out in the absence of exogenous proteolytic enzyme inhibitors, wherein the protein sample is suitable for proteomic analysis. Preferably, the protective agent consists of essentially (i) about 300 g/l to about 700 g/l imidazolidinyl urea; (ii) about 20 g/l to about 60 g/l glycine; and (iii) about 60 g/l to about 100 g/l EDTA; and the protein sample is analysed via mass spectrometry-based proteomic methods. 1. A method of preparing a protein sample for proteomic analysis , comprisinga. contacting a blood sample comprising proteins with a protective agent comprising an anticoagulant (AC) and an aldehyde releaser (AR), to obtain a mixture, optionally, wherein the blood sample is added to a blood collection tube (BCT) comprising the protective agent or the blood sample is directly drawn from a subject into a BCT comprising the protective agent, andb. isolating a fraction comprising proteins from the mixture to yield a protein sample suitable for proteomic analysis,{'claim-text': ['(I) steps (a) and (b) are carried out in the absence of exogenous proteolytic enzyme inhibitors;', '(II) the slope of the best fit line of a line graph of the number of proteins in the protein sample yielded from step (b) plotted as a function of storage time is closer to 0 compared to the slope of the best fit line of a line graph of the number of proteins in a control blood sample not contacted with a protective ...

SAMPLE PRETREATMENT DEVICE, ANALYSIS SYSTEM INCLUDING THE DEVICE, AND AUTOSAMPLER

A sample pretreatment device of an aspect of the present invention includes a conveyance mechanism () including a Z-axis guide () that linearly moves in two axes of an X axis and a Y axis and expands/contracts in a Z-axis direction on a table () where a unit that performs each step of pretreatment is arranged. The Z-axis guide () is integrally provided with a liquid handler () and a grip handler () oriented in opposite directions to each other. A side wall of a housing () on the autosampler side is provided with a sample conveyance opening (). When pretreatment of a sample ends, the Z-axis guide () is moved to a position close to the opening () in a state where a gripper () grips a pretreated plate. An arm () enters a housing of the autosampler through the opening () and an opening formed in the autosampler, and sets a plate at a predetermined position. Thus, the sample pretreatment device can eliminate the labor of the worker setting a pretreated sample in the analysis device. 1. A sample pretreatment device that performs pretreatment of a sample to be analyzed by an analysis device , the sample pretreatment device comprising:a housing which forms an outer shape of the sample pretreatment device;a sample conveyance opening formed on a wall of the housing on a side where the analysis device is positioned; anda sample conveyance unit which includes a grip unit for gripping a sample container containing a sample having been pretreated in the housing, and which moves the grip unit in the housing and moves the grip unit to an inside of a housing of the analysis device through the sample conveyance opening and an opening formed in a housing of the analysis device.2. The sample pretreatment device according to further comprising:a shutter configured to open or close the sample conveyance opening, whereinthe shutter is in an opened state when the sample conveyance unit conveys the sample container from the sample pretreatment device to the analysis device, andthe shutter ...

Flow cell for direct absorption spectroscopy

A flow cell assembly ( 16 ) for a fluid analyzer ( 14 ) that analyzes a sample ( 12 ) includes (i) a base ( 350 ) that includes a base window ( 350 B); (ii) a cap ( 352 ) having a cap window ( 352 B) that is spaced apart from the base window ( 350 B); and (iii) a gasket ( 360 ) that is secured to and positioned between the base ( 350 ) and the cap ( 352 ), the gasket ( 360 ) having a gasket body ( 360 A) that includes a gasket opening ( 360 B). The gasket body ( 360 A), the base ( 350 ) and the cap ( 352 ) cooperate to define a flow cell chamber ( 362 ). Moreover, an inlet passageway ( 366 ) extends into the flow cell chamber ( 362 ) to direct the sample ( 12 ) into the flow cell chamber ( 362 ); and an outlet passageway ( 368 ) extends into the flow cell chamber ( 362 ) to allow the sample ( 12 ) to exit the flow cell chamber ( 362 ).

METHOD FOR CANCER DIAGNOSIS AND PROGNOSIS

Disclosed herein is a method of determining whether a subject has or is at risk of developing a cancer. The method comprises, obtaining a sample from the subject; determining the levels of at least two target polypeptides, which are selected from the group consisting of, ANXA2, HSPA5, KNG1 and MMP1; and assessing whether the subject has or is at risk of developing the cancer based on the levels of target polypeptides. The present method provides a potential means to diagnose and predict the occurrence of oral squamous cell carcinoma, and accordingly, the subject in need thereof could receive a suitable therapeutic regimen in time. 131-. (canceled)32. A method for determining the concentration of at least two target polypeptides in a biological sample , wherein each of the at least two target polypeptides is selected from the group consisting of ANXA2 , HSPA5 , KNG1 and MMP1; the method comprises ,(a) selecting at least two surrogate peptides corresponding to the at least two target polypeptides, wherein each of the at least two surrogate peptides is selected from the group consisting of ANXA2 surrogate peptide, HSPA5 surrogate peptide, KNG1 surrogate peptide, and MMP1 surrogate peptide;(b) labeling the at least two surrogate peptides of step (a) by isotope;(c) digesting the biological sample by means of a proteolytic process to produce a digest;(d) adding a pre-determined concentration of the labeled versions of the surrogate polypeptides to the digest of the step (c);(e) measuring the amounts of the surrogate peptides and the labeled versions of the surrogate peptides in the mixture of step (d) by mass spectrometry;(f) dividing the measured amounts of the surrogate peptides by the measured amounts of the labeled versions of the surrogate peptides to obtain a ratio; and(g) determining the concentration of the target polypeptides in the biological sample based on the ratio of step (f) and the pre-determined concentration of the labeled versions of the surrogate ...

METHOD FOR DETECTING MONOCLONAL ANTIBODY USING MASS SPECTROMETRY

A method is provided for more easily detecting and quantifying a protein by regioselectively digesting a variable region of an Fab domain of a monoclonal antibody while suppressing proteolysis of an Fc domain. 1. A method whereina porous body in which a monoclonal antibody to be measured is immobilized in pores and nanoparticles on which a protease is immobilized are brought into contact with each other in a liquid to perform selective proteolysis of the monoclonal antibody,a resulting peptide fragment is detected using liquid chromatography-mass spectrometry (LC-MS),the porous body has an average pore diameter in a range of 10 nm-200 nm,the nanoparticles have an average particle size in a range of 50 nm-500 nm,the average particle size of the nanoparticles is larger than the average pore diameter of the porous body, anda peptide fragment to be detected has an amino acid sequence that includes an amino acid derived from a CDR2 region of a heavy chain or a light chain of the monoclonal antibody.2. The method according to claim 1 , whereinthe monoclonal antibody is trastuzumab or trastuzumab-DM1, anda detection target is a peptide having an amino acid sequence expressed in SEQ ID No: 1, 3, 6 and/or 7.3. The method according to claim 2 , wherein the detection target is detected by multiple reaction monitoring under conditions described in Table 2 or Table 3.4. The method according to claim 1 , whereinthe monoclonal antibody is bevacizumab, anda detection target is a peptide having an amino acid sequence expressed in SEQ ID No: 9-11.5. The method according to claim 4 , wherein the detection target is detected by multiple reaction monitoring under conditions described in Table 4.6. The method according to claim 1 , whereinthe monoclonal antibody is rituximab, anda detection target is a peptide having an amino acid sequence expressed in SEQ ID No: 13, 15 and/or 16.7. The method according to claim 6 , wherein the detection target is detected by multiple reaction monitoring ...

METHOD OF ANALYZING COMPOUND INCLUDING AMINE GROUP BY USING BOC COMPOUND

Provided is an amine group-derivatized composition including a Boc compound for liquid chromatography-mass spectrometry (LC-MS) analysis, and when the amine group-derivatized composition is used in analysis using reverse-phase LC-MS, it is possible to effectively analyze compounds including an amine group and an amino acid at a low cost in a short time. 2. The method of claim 1 , wherein the producing of a Boc-amine derivative is performed under microwave irradiation for about 30 seconds to about 2 minutes.3. The method of claim 1 , wherein the compound represented by Formula 1 is di-tert-butyl dicarbonate.4. The method of claim 1 , wherein the compound comprising an amine group is an amino acid.5. The method of claim 1 , wherein the analyzing of the Boc-amine derivative by using LC-MS is performed by detecting neutral loss of the compound comprising an amine group.7. The amine group-derivatized composition of claim 6 , wherein the compound represented by Formula 1 is di-tert-butyl dicarbonate. This application claims the benefits of Korean Patent Application No. 10-2016-0107775, filed on Aug. 24, 2016 and Korean Patent Application No. 10-2017-0106651, filed on Aug. 23, 2017, in the Korean Intellectual Property Office, the disclosures of which are incorporated herein in their entirety by reference.One or more embodiments include a method of analyzing a compound including an amine group using a Boc compound.The most widely used methods for amino acid analysis include a spectroscopic method, gas chromatographic-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). When these methods are used, amino acids may be analyzed with excellent sensitivity even with a small amount of a sample. However, when amino acids are analyzed by spectroscopy, there is a drawback in that standard amino acid compounds and coloring compounds must be used. GC-MS must involve derivatization of an amino acid by using a BSTFA or MSTFA reaction compound to analyze the ...

MASS SPECTROMETRY ASSAY FOR CONGENITAL ADRENAL HYPERPLASIA

Methods are provided for detecting the amount of one or more CAH panel analytes (i.e., pregnenolone, 17-OH pregnenolone, progesterone, 17-OH progesterone, dehydroepiandrosterone (DHEA), androstenedione, testosterone, deoxycorticosterone, 11-deoxycortisol, and cortisol) in a sample by mass spectrometry. The methods generally involve ionizing one or more CAH panel analytes in a sample and quantifying the generated ions to determine the amount of one or more CAH panel analytes in the sample. In methods where amounts of multiple CAH panel analytes are detected, the amounts of multiple analytes are detected in the same sample injection. 1. A method for determining the amount of 17-OH pregnanolone in a sample by mass spectrometry , the method comprising:(i) ionizing the sample under conditions suitable to produce one or more 17-OH pregnanolone ions detectable by mass spectrometry;(ii) determining by tandem mass spectrometry the amount of the one or more 17-OH pregnanolone ions; and(iii) using the determined amount of the one or more ions to determine the amount of 17-OH pregnanolone in the sample.2. The method of claim 1 , wherein the sample has been purified by liquid chromatography prior to being subjected to an ionization source.3. The method of claim 2 , wherein said liquid chromatography is high performance liquid chromatography claim 2 , ultra high performance liquid chromatography claim 2 , or turbulent flow liquid chromatography.4. The method of claim 1 , wherein the sample has been purified by solid phase extraction prior to ionization.5. The method of claim 1 , wherein an internal standard is used for determination of the amount of 17-OH pregnanolone in the sample.6. The method of claim 5 , wherein the internal standard comprises an isotopically labeled analog of 17-OH pregnanolone.7. The method of claim 1 , wherein the sample comprises plasma or serum.8. The method of claim 1 , wherein the ionizing comprises ionization by electrospray ionization (ESI).9. The ...