Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples: A tool for rapid screeningof new compounds for metabolic stability

There is a continuing need for increased throughput in the evaluation of ne w drug entities in terms of their pharmacokinetic parameters. One useful pa rameter that can be measured in vitro using liver microsomal preparations i s metabolic stability. In this report, we describe an automated system that can be used for unattended quantitative analysis of liver microsomal sampl es for a series of compounds. This system is based on the Sciex API 150 (si ngle quadrupole) liquid chromatography/mass spectrometry system and utilize s 96-well plate autosampler technology as well as a custom-designed AppleSc ript(R) which executes the on-line data processing and report generation. I t has the capability of analyzing at least 75 compounds per week or 300 com pounds per month in an automated fashion. Copyright (C) 1999 John Wiley & S ons, Ltd.