Inhou Chu and Amin A.Nomeir Pages 467 - 477 ( 11 )
A balance between pharmacological activity, safety and drug metabolism and pharmacokinetics (DMPK) at-tributes determines the fate of a new chemical entity (NCE) in drug discovery. Because of the increased number of NCEsrequiring DMPK evaluation, several in vitro higher-throughput screens and counter screens designed to evaluate DMPKattributes have been introduced in drug discovery. The DMPK screens evaluate NCEs for potential absorption, metabo-lism, drug-drug interactions, brain penetration, protein binding and pharmacokinetics. Higher-throughput analytical meth-odologies for the determination of either a common end product of a screen or the parent compound (and/or possible me-tabolites) are essential for successful DMPK screens. Because of its speed, sensitivity and specificity, liquid chromatogra-phy-tandem mass spectrometry (LC-MS/MS) has become the technology of choice for sample analysis. In this review,several in vitro screening assays that we employ in drug discovery are discussed with an e mphasis on LC-MS/MS role inaccelerating them.
LC-MS/MS, MUX, DMPK screens, drug discovery, in vitro assays, matrix effect, higher-throughput analysis
Exploratory Drug Metabo-lism, Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.