MSE with mass defect filtering for in vitro and in vivo metabolite identification
MSE with mass defect filtering for in vitro and in vivo metabolite identification
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DOI：
10.1002/rcm.2996
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发表时间：
2007-01-01
影响因子：
2
通讯作者：
Nicoll-Griffith, Deborah A.
中科院分区：
文献类型：
--
作者：
Bateman, Kevin P.;Castro-Perez, Jose;Nicoll-Griffith, Deborah A.
代谢物鉴定研究涉及候选药物生物转化产物的检测和结构表征。这些实验在整个药物发现和开发过程中都是必要的。使用高分辨率色谱法和高分辨率质谱法以及使用质量缺陷过滤的数据处理描述了体外和体内代谢物鉴定研究。使用与正交混合四极杆飞行时间质谱仪偶联的UPLC（TM）进行数据收集。该实验方法使得能够使用MSE数据收集（其中E代表碰撞能量），这在以前已被证明是代谢物鉴定研究的有力方法。使用原型质量缺陷过滤程序进行采集后处理，以消除研究样品中的内源性干扰，大大提高了代谢物的发现。该方法的简便性通过显示来自临床前大鼠药代动力学研究的血浆中代谢物的检测和结构表征的结果来说明。版权所有（c）2007约翰威利父子有限公司。
Metabolite identification studies involve the detection and structural characterization of the biotransformation products of drug candidates. These experiments are necessary throughout the drug discovery and development process. The use of high-resolution chromatography and high-resolution mass spectrometry together with data processing using mass defect filtering is described for in vitro and in vivo metabolite identification studies. Data collection was done using UPLC (TM) coupled with an orthogonal hybrid quadrupole time-of-flight mass spectrometer. This experimental approach enabled the use of MSE data collection (where E represents collision energy) which has previously been shown to be a powerful approach for metabolite identification studies. Post-acquisition processing with a prototype mass defect filtering program was used to eliminate endogenous interferences in the study samples, greatly enhancing the discovery of metabolites. The ease of this approach is illustrated by results showing the detection and structural characterization of metabolites in plasma from a preclinical rat pharmacokinetic study. Copyright (c) 2007 John Wiley & Sons, Ltd.