Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples: a tool for rapid screening of new compounds for metabolic stability.
There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic parameters. One useful parameter that can be measured in vitro using liver microsomal preparations is metabolic stability. In this report, we describe an automated system that can be used for unattended quantitative analysis of liver microsomal samples for a series of compounds. This system is based on the Sciex API 150 (single quadrupole) liquid chromatography/mass spectrometry system and utilizes 96-well plate autosampler technology as well as a custom-designed AppleScript which executes the on-line data processing and report generation. It has the capability of analyzing at least 75 compounds per week or 300 compounds per month in an automated fashion.
Korfmacher
W A
WA
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. Walter.Korfmacher@spcorp.com
Palmer
C A
CA
Nardo
C
C
Dunn-Meynell
K
K
Grotz
D
D
Cox
K
K
Lin
C C
CC
Elicone
C
C
Liu
C
C
Duchoslav
E
E
D001322:Autoanalysis; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D006801:Humans; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000737:chemistry* / Q000378:metabolism; D008970:Molecular Weight; D010599:Pharmacokinetics