Simultaneous determination of aceclofenac and three of its metabolites in human plasma by high-performance liquid chromatography.
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 10-10000 ng/mL for aceclofenac, 4'-hydroxy-aceclofenac and diclofenac, and 25-10000 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.
Hinz
Burkhard
B
Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany. hinz@pharmakologie.uni-erlangen.de
Auge
Daniel
D
Rau
Thomas
T
Rietbrock
Stephan
S
Brune
Kay
K
Werner
Ulrike
U
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; C056498:aceclofenac