High-performance liquid chromatography-atmospheric pressure photoionization/tandem mass spectrometric analysis for small molecules in plasma

被引：75

作者：

Hsieh, YS ^{[1
]}

Merkle, K

Wang, GF

Brisson, JM

Korfmacher, WA

机构：

[1] Schering Plough Res Inst, Drug Metab & Pharmacokinet Dept, Kenilworth, NJ 07033 USA

[2] Appl Biosyst Inc, Foster City, CA 94404 USA

来源：

ANALYTICAL CHEMISTRY | 2003年 / 75卷 / 13期

关键词：

D O I：

10.1021/ac0300082

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

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.

引用

页码：3122 / 3127

页数：6

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