title: Automatic mass spectrometry method development for drug discovery: application in metabolic stability assays.
abstract: 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.
authors.affiliation: Global Pharmaceutical Research and Development, Abbott Laboratories, Advanced Technologies, Dept. R4CP, Bldg. AP52-N, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Chovan
authors.forename: Candace
authors.initials: C
authors.lastname: Black-Schaefer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dandliker
authors.forename: Yau Yi
authors.initials: YY
authors.lastname: Lau
mesh_terms: 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
chemical_list: D004364:Pharmaceutical Preparations