EVALUATION OF THE STEREOSELECTIVE METABOLISM OF THE CHIRAL ANALGESIC DRUG ETODOLAC BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

The enantiomers of the racemic analgesic drug etodolac have been resol ved by fractional crystallization of the diastereomeric salts with opt ically active l-phenylethylamine. A high-performance liquid chromatogr aphic method to determine racemic etodolac (assay I) and its major met abolites (assay II) in urine using a conventional reversed-phase colum n is described. The determination of the enantiomeric ratios of etodol ac and the two metabolites 7-hydroxyetodolac and 8-(l'-hydroxyethyl)et odolac was achieved using different protein-bonded chiral stationary p hases. The urinary data for five volunteers are presented and show a m arked stereoselectivity of the metabolism of etodolac in humans.