Simultaneous determination of aceclofenac and three of its metabolites in human plasma by high-performance liquid chromatography

被引:58
作者
Hinz, B [1 ]
Auge, D [1 ]
Rau, T [1 ]
Rietbrock, S [1 ]
Brune, K [1 ]
Werner, U [1 ]
机构
[1] Univ Erlangen Nurnberg, Dept Expt & Clin Pharmacol & Toxicol, D-91054 Erlangen, Germany
关键词
phenylacetic acid derivatives; diclofenac; 4 '-hydroxyaceclofenac; 4 '-hydroxydiclofenac; metabolic conversion; pharmacokinetics;
D O I
10.1002/bmc.243
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Aceclofenac {[2-(2',6'-dichlorophenyl)amino]phenylacetoxyacetic acid} is a phenylacetic acid derivative with potent analgesic and anti-inflammatory properties and an improved gastro-intestinal tolerance. In the present study, a liquid-liquid extraction-based reversed-phase HPLC method with UV detection was validated and applied for the analysis of aceclofenac and three of its metabolites (4'-hydroxy-aceclofenac, diclofenac, 4'-hydroxy-diclofenac) in human plasma. The analytes were separated using an acetonitrile phosphate buffer gradient at a flow rate of 1 mL/min, and UV detection at 282 nm. The retention times for aceclofenac, diclofenac, 4'-hydroxy-aceclofenac, 4'-hydroxy-diclofenac and ketoprofen (internal standard) were 69.1, 60.9, 46.9 28.4 and 21.2 min, respectively. The validated quantitation range of the method was 10-10,000 ng/mL for aceclofenac, 4'-hydroxy-aceclofenac and diclofenac, and 25-10,000 ng/mL for 4'-hydroxy-diclofenac. The developed procedure was applied to assess the pharmacokinetics of aceclofenac and its metabolites following administration of a single 100 mg oral dose of aceclofenac to three healthy male volunteers. Copyright (C) 2003 John Wiley Sons, Ltd.
引用
收藏
页码:268 / 275
页数:8
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