THE DIRECT DETERMINATION OF THE ENANTIOMERS OF KETOROLAC AND PARAHYDROXYKETOROLAC IN PLASMA AND URINE USING ENANTIOSELECTIVE LIQUID-CHROMATOGRAPHY ON A HUMAN SERUM ALBUMIN-BASED CHIRAL STATIONARY-PHASE

An enantioselective assay has been developed for the determination of the enantiomers of ketorolac and its metabolite p-hydroxyketorolac in plasma and urine. The analytical method utilizes a coupled achiral-chiral HPLC system where the initial separation of ketorolac from p-hydroxyketorolac and matrix interferences was achieved on a C-18-stationary phase and the enantioselective separations of the two target solutes were accomplished on a human serum albumin-based chiral stationary phase. The two columns were attached in sequence and the assay was carried out without the necessity of column-switching techniques. The method has been validated for use in pharmacokinetic and metabolic studies and represents the initial report of the determination of ketorolac and p-hydroxyketorolac enantiomers in urine. The results of the study indicate that after the administration of racemic ketorolac there was an enantioselective distribution of ketorolac enantiomers in plasma [(R)-ketorolac: (S)-ketorolac = 3.89 +/- 0.93 (n = 6) and urine (R)-ketorolac: (S)-ketorolac = 1.26 +/- 0.09 (n = 7)]. The mean ratio of the p-hydroxyketorolac enantiomers was 1.77 +/- 0.46 (n = 7). Both ketorolac and p-hydroxyketorolac are glucuronized in the acyl carboxyl moiety and the results of this study indicate that this process is not enantiospecific. (C) 1994 Wiley-Liss, Inc.