Investigation of the pharmacokinetics of celecoxib by liquid chromatography-mass spectrometry

Abstract

A new method for the quantification of celecoxib in human plasma based on reversed-phase high-performance liquid chromatography (HPLC) coupled to atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) after liquid-liquid extraction is presented. The method is rapid, sensitive and highly selective. The retention time of celecoxib was 2.3 min. The limit of quantification was 5 μg/L. Rofecoxib was used as internal standard. After validation, the method was used to study the pharmacokinetic profile of celecoxib following administration of a single oral dose (200 mg) in 12 healthy volunteers. Since celecoxib should be metabolized primarily by cytochrome 2C9 (CYP2C9), a poor metabolizer (PM) for this cytochrome P450 enzyme was included in the study. Pharmacokinetic characteristics (mean ± SD) of extensive metabolizers (EM) were tmax 2.9 ± 1.2 h, cmax 842 ± 280 μg/L, AUC∞ 6246 ± 2147 μg h/L and t1/2 7.8 ± 2.7 h. The area under the curve (AUC∞) for the PM was 12561 μg h/L. However, we found no noticeable increase in half life in the PM (11.5 h) after a single dose of celecoxib. Copyright © 2001 John Wiley & Sons, Ltd.