Evaluation of Deuterium Labeled and Unlabeled Bis-methyl Glutathione Combined with Nano liquid Chromatography Mass Spectrometry to Screen and Characterize Reactive Drug Metabolites
Evaluation of Deuterium Labeled and Unlabeled Bis-methyl Glutathione Combined with Nano liquid Chromatography Mass Spectrometry to Screen and Characterize Reactive Drug Metabolites
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DOI：
10.1021/tx1003694
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发表时间：
2011-03-01
影响因子：
4.1
通讯作者：
Klarskov, Klaus
中科院分区：
文献类型：
--
作者：
Defoy, Daniel;Dansette, Patrick M.;Klarskov, Klaus
我们提出了一种基于使用氘标记/未标记的双甲基谷胱甘肽（GSH）酯（GSH（CH 3/CD 3）（2））和纳米液体电喷雾电离色谱法c）与谷胱甘肽在线耦合的反应性代谢物检测试验，羧酸基团串联质谱法（nLC-ESI-MS/MS）。通过酯化进行比较，引入了6的质量差，这有助于鉴定捕获的代谢物，并提高了正离子化模式下质谱信号的强度。肽允许捕获通过与对乙酰氨基酚、卡马西平（CBZ）NADPH和微粒体孵育在体外产生的软亲电反应性代谢物。
We present a reactive metabolite detection assay based on the use of deuterium labeled/unlabeled bis-methyl glutathione (GSH) esters (GSH(CH3/CD3)(2)) and nanoliquid electrospray ionization chromatography c)coupled online with with glutathione, neutralization of the; carboxylic acid groups tandem mass spectrometry (nLC-ESI-MS/MS). Compared by esterification introduced a mass difference of 6, which facilitated the identification of trapped metabolites and improved the intensity of the mass spectrometry signal in positive ionization mode. The peptides allowed for the trapping of soft electrophilic reactive metabolites generated in vitro by incubation with acetaminophen, carbamazepine (CBZ) NADPH, and microsomes.