A multiplexed targeted assay for high-throughput quantitative analysis of serum methylamines by ultra performance liquid chromatography coupled to high resolution mass spectrometry

被引:13
作者
Kadar, Hanane [1 ,2 ]
Dubus, Justine [2 ]
Dutot, Jeremie [1 ,3 ]
Hedjazi, Lyamine [2 ]
Srinivasa, Suman [3 ,4 ]
Fitch, Kathleen V. [3 ,4 ]
Grinspoon, Steven K. [3 ,4 ]
Nicholson, Jeremy K. [5 ,6 ]
Dumas, Marc-Emmanuel [5 ,6 ]
Gauguier, Dominique [1 ,5 ]
机构
[1] Univ Paris 06, Sorbonne Univ, Univ Paris Descartes, Sorbonne Paris Cite,INSERM,UMR S 1138,Cordeliers, 15 Rue Ecole Med, F-75006 Paris, France
[2] Univ Paris 06, Inst Cardiometabol & Nutr, Hosp Pitie Salpetriere, 58 Blvd Hop, F-75013 Paris, France
[3] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA
[4] Harvard Univ, Sch Med, Boston, MA 02114 USA
[5] Univ London Imperial Coll Sci Technol & Med, Sect Biomol Med, Div Computat Syst Med, Dept Surg & Canc, Sir Alexander Fleming Bldg,Exhibit Rd, London SW7 2AZ, England
[6] Univ London Imperial Coll Sci Technol & Med, MRC NIHR Natl Phenome Ctr, Dept Surg & Canc, IRDB Bldg,Du Cane Rd, London W12 0NN, England
关键词
Trimethylamine; Trimethylamine-N-oxide; Choline; Betaine; L-carnitine; Cardiometabolic diseases; TRIMETHYLAMINE-N-OXIDE; ELECTROSPRAY-IONIZATION; URINARY TRIMETHYLAMINE; L-CARNITINE; METABOLISM; MICROBIOTA; CHOLINE; PLASMA; GENE;
D O I
10.1016/j.abb.2016.03.029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable "methylamine panel" method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and L-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS). Metabolite separation was carried out on a HILIC stationary phase. For all metabolites, the assay was linear in the range of 0.25-12.5 mu mol/L and enabled to reach limit of detection of about 0.10 mu mol/L. Relative standard deviations were below 16% for the three levels of concentrations. We demonstrated the strong reliability and robustness of the method, which was applied to serum samples from healthy individuals to establish the range of concentrations of the metabolites and their correlation relationships and detect gender differences. Our data provide original information for implementing in a clinical environment a MS-based diagnostic method with potential for targeted metabolic screening of patients at risk of cardiometabolic diseases. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:12 / 20
页数:9
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