title: Stereoselective analysis of fenoprofen and its metabolites.
abstract: Reversed-phase high-performance liquid chromatographic assays have been developed to quantitate simultaneously fenoprofen and its major metabolites as well as to distinguish between their R- and S- enantiomers following a single oral dose of 600 mg racemic fenoprofen to healthy volunteers. The compounds are extracted from plasma (after precipitation of plasma protein) or assayed directly in diluted urine samples employing a gradient solution on a C18 column and ultraviolet detection. Two internal standards, ketoprofen and flunoxaprofen, are used to allow measurement of very low (0.05 microgram/ml) and high (70 microgram/ml) concentrations in each sample. R- and S-fenoprofen glucuronides can be separated directly; the 4'-hydroxyfenoprofen conjugates are measured via an indirect method by comparing the concentration of 4'-hydroxyfenoprofen before and after hydrolysis. The R- and S-enantiomers of both parent and 4'-hydroxy metabolite are derivatized with L-leucinamide via an ethyl chloroformate intermediate and subsequently analyzed on a C18 column. Concentrations of metabolites found in plasma were low when compared to parent drug. The S/R ratio of fenoprofen in plasma always exceeds 1 and increases with time after dosage while the S/R ratio of its 4'-hydroxy metabolite remains almost unchanged at 1.1. R-Fenoprofen glucuronide disappears rapidly from plasma as compared to its S-antipode; a less pronounced difference is noted between R- and S-4'-hydroxyfenoprofen conjugates. Fenoprofen is almost completely excreted as its S-acyl glucuronides; the renal clearance of unchanged drug is very low.
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of California San Francisco 94143-0446.
authors.forename: C
authors.initials: C
authors.lastname: Volland
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: L Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005279:Fenoprofen / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D005279:Fenoprofen