Potential of HILIC-MS in quantitative bioanalysis of drugs and drug metabolites.
One fundamental requirement for many lead optimization processes is the need for bioanalytical support within pharmaceutical drug discovery and development. Currently, most bioanalytical methods for pharmaceutical analysis employ HPLC coupled with MS/MS. The combination of HPLC and MS/MS detection frequently offers the complete resolution of the dosed compounds from their metabolites and the endogenous interferences to avoid extra efforts for chemical separation and sample clean-up procedures resulting in higher-throughput assays for a series of new chemical entities (NCEs). Hydrophilic interaction chromatography (HILIC) has been demonstrated to be a powerful technique for the retention of polar analytes offering a difference in selectivity compared to traditional RP chromatography. This review summarizes the HILIC-MS/MS methods for the trace quantitative determinations of the drug compounds and their metabolites to support both in vitro and in vivo experiments. The challenges on performing HILIC-MS/MS assays such as matrix ionization suppression and the potential for endogenous interferences are also presented.
Hsieh
Yunsheng
Y
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ, USA. yunsheng.hsieh@spcorp.com
D001274:Atmospheric Pressure; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000378:metabolism; D044367:Phase Transition; D012822:Silicon Dioxide; D012997:Solvents; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D014867:Water
D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; D012822:Silicon Dioxide