High-performance liquid chromatographic determination of loxoprofen and its diastereomeric alcohol metabolites in biological fluids by fluorescence labelling with 4-bromomethyl-6,7-methylenedioxycoumarin.
A simple and sensitive high-performance liquid chromatographic procedure to determine loxoprofen and its diastereomeric alcohol metabolites in biological specimens is described. The analysis involves liquid-liquid extraction with benzene, pre-column derivatization with a highly fluorogenic reagent, 4-bromomethyl-6,7-methylenedioxycoumarin (BrMDC) and subsequent separation on a reversed-phase column. Loxoprofen, its pharmacologically active metabolite, trans-alcohol, and less active cis-alcohol were completely separated within 20 min with a mobile phase of 55% of aqueous acetonitrile containing acetic acid. Any endogenous substances do not interfere in the analysis of either plasma or urine samples. The quantitation limit was 0.01 micrograms/ml for human plasma and 0.05 micrograms/ml for urine. The method was applied to a pharmacokinetic study in healthy human subjects who had received 60 mg of loxoprofen sodium.
Naganuma
H
H
Product Development Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Kawahara
Y
Y
D000328:Adult; D000438:Alcohols / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins; D005456:Fluorescent Dyes; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010666:Phenylpropionates / Q000032:analysis* / Q000493:pharmacokinetics; D013237:Stereoisomerism
D000438:Alcohols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003374:Coumarins; D005456:Fluorescent Dyes; D010666:Phenylpropionates; C040656:loxoprofen; C067663:4-bromomethyl-6,7-methylenedioxycoumarin