The role of hyphenated chromatography-mass spectrometry techniques in exploratory drug metabolism and pharmacokinetics.
The advances in high-speed synthesis technologies have produced a large number of biologically active new chemical entities (NCEs) for developability assessment. Current drug discovery efforts have been focused on identifying drug metabolism and pharmacokinetic (DMPK) issues at the earliest possible stage in order to reduce the attrition rate of drug candidates during the development phase. Mass spectrometry (MS) has proven a powerful tool in providing rapid qualitative and quantitative measurements of drug molecules for DMPK studies in both drug discovery and development. Although mass spectrometers can serve as separation devices, for most pharmaceutical applications, some form of chromatography is combined with MS. For most MS-based methods, tandem mass spectrometry (MS/MS) utilizes atmospheric pressure ionization (API) and chromatographic techniques. This review describes the major hyphenated chromatography-mass spectrometry techniques and their applications in supporting exploratory DMPK studies including various in vitro and in vivo PK and metabolite identification profiles.
Hsieh
Yunsheng
Y
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. yunsheng.hsieh@spcorp.com
Korfmacher
Walter
W
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002845:Chromatography / Q000295:instrumentation / Q000379:methods*; D015195:Drug Design; D006801:Humans; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
D004364:Pharmaceutical Preparations