Automatic mass spectrometry method development for drug discovery: application in metabolic stability assays

被引:35
作者
Chovan, LE [1 ]
Black-Schaefer, C [1 ]
Dandliker, PJ [1 ]
Lau, YY [1 ]
机构
[1] Abbott Labs, Adv Technol Dept, Global Pharmaceut Res & Dev, Dept R4CP, N Chicago, IL 60064 USA
关键词
D O I
10.1002/rcm.1735
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
High-throughput metabolic screening has been requested routinely to keep pace with high-throughput organic synthesis. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) with a fast gradient has become the method of choice for the task due to its sensitivity and selectivity. We have developed an automated system that consists of a robotic system for in vitro incubation and a commercially available software package for automatic MS/MS method development. A short, generic LC gradient and MS conditions that are applicable to most compounds have been developed to minimize the method development time and data analysis. This system has been used to support a number of in vitro screening assays in early drug discovery phase including microsomal stability and protein binding. Copyright (C) 2004 John Wiley Sons, Ltd.
引用
收藏
页码:3105 / 3112
页数:8
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