High performance capillary electrophoresis for determination of the enantiomers of 2-arylpropionic acid derivatives in human serum. Pharmacokinetic studies of ketoprofen enantiomers following administration of standard and sustained release tablets.

A stereospecific capillary zone electrophoresis (CZE) method for determination of the enantiomers of some 2-arylpropionic acid derivatives (2-APA, profens) in human serum has been developed. Racemic-ibuprofen (rac-IBP), racemic-flurbiprofen (rac-FBP), racemic-ketoprofen (rac-KTP) and (+)-S-naproxen ((+)-S-NPX--an internal standard) were chosen for these studies. The 2-APA enantiomers were extracted from acidified serum samples using methylene chloride separated in a fused silica capillary. The capillary was filled with a background electrolyte, which consisted of 0.05 M heptakis 2,3,6-tri-O-methyl-beta-cyclodextrin (TMbetaCD) (chiral selector) in 0.02 M triethanolamine-phosphate buffer of pH 5.0. Separation and resolution of the enantiomer mixture were obtained in one analytical run. The calculated electrophoretic parameters of the analytes were as follows: electrophoretic mobility, micorep(-)-R = -0.75 x 10(-4) to -0.30 x 10(-4) cm2/Vs; micorep(+)-S = -0.83 -(-0.38) cm2/Vs and electroosmotic mobility, microEOF = 2.35 x 10(-4) cm2/Vs, migration times, tmigr R = 12.55 - 16.07 min; tmigr s = 13.08 - 16.9 min, resolution factors, RS = 1.88 - 3.70 and chiral selectivity, alpha = 1.16 - 1.34. The method developed for the enantiomers was validated. The calibration curves were linear in the range of 0.5-50.0 microg/ml for FBP or KTP and of 1.0-50.0 microg/ml for IBP enantiomer concentrations. Recovery of the enantiomers from serum was about 90%. At the limit of quantification (LOQ) precision and accuracy were within 15%. The validated method was successfully applied to pharmacokinetic and bioavailability studies on KTP enantiomers in humans after administration of standard and sustained release tablets of rac-KTP. Significant differences in the pharmacokinetic parameters of both formulations were observed and the studied formulations were not bioequivalent.