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The direct determination of the enantiomers of ketorolac and para hydroxyketorolac in plasma and urine using enantioselective liquid chromatography on a human serum albumin‐based chiral stationary phase
Author(s) -
DiazPerez Maria J.,
Chen John C.,
Aubry AnneFrancoise,
Wainer Irving W.
Publication year - 1994
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530060411
Subject(s) - ketorolac , chemistry , enantiomer , chromatography , enantioselective synthesis , urine , metabolite , high performance liquid chromatography , chiral stationary phase , pharmacokinetics , chiral column chromatography , stereochemistry , pharmacology , organic chemistry , biochemistry , analgesic , medicine , catalysis
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. © 1994 Wiley‐Liss, Inc.