Automatic mass spectrometry method development for drug discovery: application in metabolic stability assays.
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.
Chovan
Linda E
LE
Global Pharmaceutical Research and Development, Abbott Laboratories, Advanced Technologies, Dept. R4CP, Bldg. AP52-N, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA.
Black-Schaefer
Candace
C
Dandliker
Peter J
PJ
Lau
Yau Yi
YY
D001331:Automation; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004355:Drug Stability; D013058:Mass Spectrometry / Q000379:methods*; D008861:Microsomes / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D012680:Sensitivity and Specificity
D004364:Pharmaceutical Preparations