CA2783797C - Mass spectrometric determination of non-derivatized, non-metabolized vitamin d - Google Patents

Mass spectrometric determination of non-derivatized, non-metabolized vitamin d Download PDF

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Publication number
CA2783797C
CA2783797C CA2783797A CA2783797A CA2783797C CA 2783797 C CA2783797 C CA 2783797C CA 2783797 A CA2783797 A CA 2783797A CA 2783797 A CA2783797 A CA 2783797A CA 2783797 C CA2783797 C CA 2783797C
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Prior art keywords
vitamin
ions
sample
column
metabolized
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French (fr)
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CA2783797A1 (en
Inventor
Brett Holmquist
Nigel J. Clarke
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Quest Diagnostics Investments LLC
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Quest Diagnostics Investments LLC
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/82—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving vitamins or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/14—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers
    • H01J49/145—Ion sources; Ion guns using particle bombardment, e.g. ionisation chambers using chemical ionisation
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N2030/009—Extraction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Plasma & Fusion (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
CA2783797A 2009-12-11 2010-12-09 Mass spectrometric determination of non-derivatized, non-metabolized vitamin d Active CA2783797C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US28593809P 2009-12-11 2009-12-11
US28594309P 2009-12-11 2009-12-11
US61/285,938 2009-12-11
US61/285,943 2009-12-11
PCT/US2010/059765 WO2011072163A1 (en) 2009-12-11 2010-12-09 Mass spectrometric determination of non-derivatized, non-metabolized vitamin d

Publications (2)

Publication Number Publication Date
CA2783797A1 CA2783797A1 (en) 2011-06-16
CA2783797C true CA2783797C (en) 2021-06-08

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA2783797A Active CA2783797C (en) 2009-12-11 2010-12-09 Mass spectrometric determination of non-derivatized, non-metabolized vitamin d

Country Status (6)

Country Link
US (8) US20110240840A1 (https=)
EP (1) EP2510339B1 (https=)
JP (3) JP6113504B2 (https=)
CN (1) CN102753964A (https=)
CA (1) CA2783797C (https=)
WO (2) WO2011072168A1 (https=)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7745226B2 (en) * 2005-04-06 2010-06-29 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites
US7972868B2 (en) 2007-11-28 2011-07-05 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US7977117B2 (en) 2009-12-03 2011-07-12 Quest Diagnostics Investments Incorprated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
CN102812356B (zh) 2009-12-11 2017-08-08 奎斯特诊断投资公司 多重样品中的甾族化合物的质谱法
US20110240840A1 (en) 2009-12-11 2011-10-06 Quest Diagnostics Investments Incorporated Mass spectrometric determination of cookson-derivatized, non-metabolized vitamin d
EP2528443B1 (en) * 2010-01-25 2017-01-11 DH Technologies Development Pte. Ltd. Quantitative analysis of vitamin d3, vitamin d2, and metabolites thereof
WO2014149847A2 (en) 2013-03-15 2014-09-25 Riaz Abrar Ionization within ion trap using photoionization and electron ionization
US20160282371A1 (en) * 2015-03-28 2016-09-29 Quantalytical Labs Inc. Solid Phase Extraction, Derivatization with Crown Ethers, and Mass Spectrometry, Methods, Reagents and Kits
CN105403631B (zh) * 2015-10-28 2017-12-08 浙江省疾病预防控制中心 一种快速检测保健食品中维生素d3含量的方法
WO2018198043A1 (en) * 2017-04-28 2018-11-01 Waters Technologies Corporation Methods for quantifying total vitamin d
US20210088486A1 (en) * 2018-01-29 2021-03-25 Dh Technologies Development Pte. Ltd. Methods and systems for detection of vitamin d metabolites
CN111999372A (zh) * 2020-07-09 2020-11-27 山东师范大学 可高通量筛选喹喔啉衍生物合成条件的微液滴电喷雾装置及方法
WO2023155000A1 (en) * 2022-02-15 2023-08-24 Mcmaster University High throughput rapid screening of vitamin d

Family Cites Families (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3030084A (en) 1958-11-06 1962-04-17 Tillotson Mfg Co Charge forming apparatus
US4332591A (en) * 1978-01-19 1982-06-01 Sumitomo Chemical Company, Limited Analytical method and apparatus for the determination of total nitrogen contents in aqueous systems
US5030772A (en) 1990-02-14 1991-07-09 Deluca Hector F Process for preparing vitamin D2 compounds and the corresponding 1 α-hydroxylated derivatives
US5605798A (en) 1993-01-07 1997-02-25 Sequenom, Inc. DNA diagnostic based on mass spectrometry
JPH06341980A (ja) 1993-02-24 1994-12-13 Kureha Chem Ind Co Ltd ビタミンｄ３誘導体の定量法
ATE242485T1 (de) 1993-05-28 2003-06-15 Baylor College Medicine Verfahren und massenspektrometer zur desorption und ionisierung von analyten
JP2968910B2 (ja) 1993-07-14 1999-11-02 ヤマサ醤油株式会社 １α，２５（ＯＨ）２ビタミンＤ３に対する抗体及びその用途
WO1995033279A1 (en) 1994-05-31 1995-12-07 University Of Warwick Tandem mass spectrometry apparatus
DE19531152A1 (de) 1994-12-15 1996-06-20 Bayer Ag Substituierte N-Aryl-Stickstoffheterocyclen
US5614408A (en) * 1995-10-18 1997-03-25 The United States Of America As Represented By The Secretary Of Agricultural Monoclonal antibodies to potato, tomato, and eggplant glycoalkaloids and assays for the same
US5772874A (en) 1995-11-02 1998-06-30 Cohesive Technologies, Inc. High performance liquid chromatography method and apparatus
WO1997026532A1 (en) 1996-01-19 1997-07-24 Cohesive Technologies, Inc. High performance liquid chromatography method and apparatus
DE69738206T2 (de) 1996-11-06 2008-07-17 Sequenom, Inc., San Diego DNA-Diagnostik mittels Massenspektrometrie
US5916523A (en) * 1996-12-04 1999-06-29 Antek Instruments, Inc. Methods for near simultaneous chemiluminescent sulfur and nitrogen detection
AU7497798A (en) * 1997-05-16 1998-12-08 F. Hoffmann-La Roche Ag 3-epi compounds of vitamin d3 and uses thereof
GB9717926D0 (en) 1997-08-22 1997-10-29 Micromass Ltd Methods and apparatus for tandem mass spectrometry
GB9719187D0 (en) 1997-09-09 1997-11-12 Glaxo Group Ltd Compounds
JP2002502086A (ja) 1998-01-23 2002-01-22 アナリティカ オブ ブランフォード インコーポレーテッド 表面からの質量分光測定
WO1999067211A1 (de) 1998-06-25 1999-12-29 Immundiagnostik Gesellschaft Für Produktion Und Vertrieb Von Labordiagnostika Mbh FUNKTIONELLE VITAMIN-D-DERIVATE UND VERFAHREN ZUR BESTIMMUNG VON 25-HYDROXY- UND 1α,25-DIHYDROXY-VITAMIN-D
US20020045606A1 (en) 1999-12-02 2002-04-18 Reddy Satyanarayana G. Esters of vitamin D3 and uses thereof
GB0029729D0 (en) 2000-12-06 2001-01-17 Ids Ltd Method for detection of vitamin D metabolites
US7087395B1 (en) 2001-01-16 2006-08-08 Quest Diagnostics Investments Incorporated Vitamin D assay
WO2003046148A2 (en) 2001-11-29 2003-06-05 Thermo Finnigan Llc Polypeptide quantitation
WO2004002996A1 (ja) 2002-06-27 2004-01-08 Chugai Seiyaku Kabushiki Kaisya フェロセン化合物およびその用途
EP2186879B1 (en) 2002-10-03 2016-11-23 Norman Leigh Anderson High sensitivity quantitation of peptides by mass spectrometry
US7632686B2 (en) 2002-10-03 2009-12-15 Anderson Forschung Group High sensitivity quantitation of peptides by mass spectrometry
CA2519626C (en) 2003-04-14 2013-06-18 Georgetown University Thyroid hormone analysis by mass spectrometry with minimal sample preparation
WO2004090525A1 (en) * 2003-04-14 2004-10-21 Georgetown University Steroid hormone analysis by mass spectrometry
US6977143B1 (en) 2003-09-08 2005-12-20 Quest Diagnostics Investments Incorporated Determination of testosterone by mass spectrometry
CA2545685A1 (en) * 2003-11-14 2005-06-02 Irm Llc Fluorous labeling for selective processing of biologically-derived samples
JP4555994B2 (ja) 2003-12-19 2010-10-06 日立化成工業株式会社 バックライト装置及び液晶表示装置
BRPI0418756A (pt) 2004-05-19 2007-09-11 Merck & Co Inc composições e métodos para inibir a reabsorção óssea
CA2480549A1 (fr) 2004-09-15 2006-03-15 Phytronix Technologies Inc. Source d'ionisation pour spectrometre de masse
US20060094039A1 (en) 2004-09-20 2006-05-04 Ron Rosenfeld Diagnosis of fetal aneuploidy
US7700365B2 (en) 2004-10-29 2010-04-20 Mayo Foundation For Medical Education And Research Vitamin D deficiencies
US20070037286A1 (en) 2005-02-09 2007-02-15 Subhasish Purkayastha Thyroxine-containing compound analysis methods
WO2006107339A2 (en) 2005-03-31 2006-10-12 Georgetown University Free thyroxine and free triiodothyronine analysis by mass spectrometry
US7972867B2 (en) * 2005-04-06 2011-07-05 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
EP1886112B1 (en) 2005-04-06 2014-07-09 Washington University St. Louis Methods for measuring the metabolism of neurally derived biomolecules in vivo
US7745226B2 (en) 2005-04-06 2010-06-29 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites
US20060236886A1 (en) 2005-04-20 2006-10-26 Agfa-Gevaert Process for the offset printing of a catalytic species via a hydrophilic phase
JP2009509992A (ja) 2005-09-29 2009-03-12 エフ．ホフマン−ラ ロシュ アーゲー ２５−ヒドロキシビタミンｄに対する抗体
US20070105179A1 (en) 2005-11-09 2007-05-10 Dionex Corporation Methods of detecting N-and O-linked oligosaccharides in glycoproteins
US7855057B2 (en) 2006-03-23 2010-12-21 Millipore Corporation Protein splice variant/isoform discrimination and quantitative measurements thereof
US7989760B2 (en) 2006-05-24 2011-08-02 SWCE Inc. Extraction detection system and method
US7935921B2 (en) * 2006-05-26 2011-05-03 Laboratory Corporation Of America Holdings Methods and systems for the quantitative analysis of biomarkers
CA2649338C (en) 2006-06-06 2011-07-12 F.Hoffman-La Roche Ag Improved measurement of vitamin d
US7906341B2 (en) 2006-06-30 2011-03-15 Dh Technologies Development Pte, Ltd. Methods, mixtures, kits and compositions pertaining to analyte determination
WO2008027861A1 (en) 2006-08-30 2008-03-06 Ge Healthcare Bio-Sciences Corp. System and method for characterizing membranes and membrane filtration devices
US7999084B2 (en) * 2007-05-16 2011-08-16 Agilent Technologies, Inc. Devices and methods for reducing matrix effects
US7807172B2 (en) 2007-06-13 2010-10-05 University Of Washington Methods and compositions for detecting thyroglobulin in a biological sample
JP4883540B2 (ja) 2007-06-21 2012-02-22 国立大学法人福井大学 同位体化合物を標識として使用するタンパク質の分析方法
JP5080945B2 (ja) 2007-11-09 2012-11-21 株式会社日立ハイテクノロジーズ 質量分析装置および質量分析方法
US7972868B2 (en) 2007-11-28 2011-07-05 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US8030084B2 (en) 2007-12-06 2011-10-04 Quest Diagnostics Investments Incorporated Thyroglobulin quantitation by mass spectrometry
WO2010019566A2 (en) 2008-08-11 2010-02-18 Mayo Foundation For Medical Education And Research Methods for determining levels of 1,25 dihydroxy vitamin d2 and d3
WO2010099108A2 (en) 2009-02-24 2010-09-02 Mayo Foundation For Medical Education And Research Multiplexing derivatized anayltes using mass spectroscopy
US7977117B2 (en) * 2009-12-03 2011-07-12 Quest Diagnostics Investments Incorprated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
US8034627B2 (en) 2009-12-03 2011-10-11 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
CN102812356B (zh) 2009-12-11 2017-08-08 奎斯特诊断投资公司 多重样品中的甾族化合物的质谱法
US20110240840A1 (en) 2009-12-11 2011-10-06 Quest Diagnostics Investments Incorporated Mass spectrometric determination of cookson-derivatized, non-metabolized vitamin d
EP2528443B1 (en) 2010-01-25 2017-01-11 DH Technologies Development Pte. Ltd. Quantitative analysis of vitamin d3, vitamin d2, and metabolites thereof
EP2548015A1 (en) 2010-03-15 2013-01-23 Anderson Forschung Group, Inc. Improved mass spectrometric assays for peptides
WO2012058614A1 (en) 2010-10-29 2012-05-03 Cohesive Technologies Inc. Lc-ms separation and detection of vitamin d metabolites
JPWO2012111249A1 (ja) 2011-02-14 2014-07-03 学校法人麻布獣医学園 質量分析法における質量変化を検出する方法及び安定同位体標識タンパク質の絶対量の定量方法
US9140695B2 (en) 2012-01-18 2015-09-22 University Of Utah Research Foundation Methods for analysis of free and autoantibody-bound biomarkers and associated compositions, devices, and systems
WO2014047316A1 (en) 2012-09-20 2014-03-27 Quest Diagnostics Investments Incorporated Thyroglobulin quantitation by mass spectroscopy
JP7209363B2 (ja) 2020-04-13 2023-01-20 リオモ インク スタビリティ評価システム、プログラム及び方法

Also Published As

Publication number Publication date
EP2510339B1 (en) 2019-09-18
JP2013513802A (ja) 2013-04-22
US20180348236A1 (en) 2018-12-06
JP6113504B2 (ja) 2017-04-12
US20170115314A1 (en) 2017-04-27
US20120025067A1 (en) 2012-02-02
JP2016026287A (ja) 2016-02-12
JP6290145B2 (ja) 2018-03-07
US11852636B2 (en) 2023-12-26
JP6728254B2 (ja) 2020-07-22
WO2011072163A1 (en) 2011-06-16
US20240077503A1 (en) 2024-03-07
US20220214366A1 (en) 2022-07-07
CA2783797A1 (en) 2011-06-16
JP2018105878A (ja) 2018-07-05
US11280799B2 (en) 2022-03-22
US20110240840A1 (en) 2011-10-06
WO2011072168A1 (en) 2011-06-16
US11549954B2 (en) 2023-01-10
EP2510339A1 (en) 2012-10-17
US20230146212A1 (en) 2023-05-11
US10753950B2 (en) 2020-08-25
EP2510339A4 (en) 2013-11-27
US20210041464A1 (en) 2021-02-11
CN102753964A (zh) 2012-10-24

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