Simultaneous fast HPLC-MS/MS analysis of drug candidates and hydroxyl metabolites in plasma.
A rapid bioanalytical method was evaluated for the simultaneous determination of drug discovery compounds and their potential metabolites in plasma samples within 1 min run time by fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The fast HPLC-MS/MS system is achieved by using mini-column HPLC coupled to tandem mass spectrometer which is advantageous over regular HPLC-MS/MS systems, such as a shorter chromatographic region of ionization suppression, less solvent consumption and higher throughput. Matrix ionization suppression effect of the test compounds in plasma samples when using fast HPLC-MS/MS method was examined by a post-column infusion technique. In the described example, the proposed approach has been successfully employed to determine the plasma concentration of the test compound and its hydroxyl metabolite (M+16) in monkey in the low ng/ml region. The monkey pharmacokinetic results obtained by the proposed fast HPLC-MS/MS method were in good agreement within 20% error with those obtained by the regular HPLC-MS/MS method based on the same sample preparation procedure.
Hsieh
Yunsheng
Y
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. yunsheng.hsieh@spcorp.com
Brisson
Jean-Marc
JM
Wang
Ganfeng
G
Ng
Kwokei
K
Korfmacher
Walter A
WA
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D000882:Haplorhini; D006900:Hydroxylation; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000097:blood; D051381:Rats; D012015:Reference Standards; D012996:Solutions
D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D012996:Solutions