High-performance liquid chromatography-atmospheric pressure photoionization/tandem mass spectrometric analysis for small molecules in plasma.
A generic high-performance liquid chromatography (HPLC) system interfaced with an atmospheric pressure photoionization (APPI) source and a tandem mass spectrometer was developed for the quantitative determination of small molecules in plasma in support of exploratory in vivo pharmacokinetics. This report summarizes the effects of variations in reversed-phase mode HPLC conditions such as mobile-phase flow rate, solvent composition, organic modifier content, and nebulizer temperature on the photoionization efficiency of both clozapine and lonafarnib. The matrix ionization suppression effect on this method was investigated using the postcolumn infusion technique. The procedure was used to quantitate plasma levels following oral administration of 42 drug discovery compounds to rats. The pharmacokinetic results of 42 drug discovery compounds in rats evaluated by both APPI and atmospheric pressure chemical ionization interfaces were found to be well correlated.
Hsieh
Yunsheng
Y
Drug Metabolism and Pharmacokinetics Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. yunsheng.hsieh@spcorp.com
Merkle
Kara
K
Wang
Ganfeng
G
Brisson
Jean-Marc
JM
Korfmacher
Walter A
WA
D000284:Administration, Oral; D000818:Animals; D001274:Atmospheric Pressure; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003024:Clozapine / Q000097:blood* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015507:Drugs, Investigational / Q000032:analysis* / Q000493:pharmacokinetics; D013058:Mass Spectrometry / Q000379:methods*; D010777:Photochemistry; D010880:Piperidines / Q000097:blood* / Q000737:chemistry; D011725:Pyridines / Q000097:blood* / Q000737:chemistry; D051381:Rats; D003986:Dibenzocycloheptenes
D003024:Clozapine; D015507:Drugs, Investigational; D010880:Piperidines; D011725:Pyridines; C115354:lonafarnib; D003986:Dibenzocycloheptenes