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Automatic mass spectrometry method development for drug discovery: application in metabolic stability assays
Author(s) -
Chovan Linda E.,
BlackSchaefer Candace,
Dandliker Peter J.,
Lau Yau Yi
Publication year - 2004
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1735
Subject(s) - chemistry , chromatography , drug discovery , tandem mass spectrometry , mass spectrometry , liquid chromatography–mass spectrometry , throughput , metabolic stability , in vitro , biochemistry , computer science , telecommunications , wireless
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 © 2004 John Wiley & Sons, Ltd.