STEREOSELECTIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY FOR THE DETERMINATION OF SOTALOL ENANTIOMERS IN BIOLOGICAL-FLUIDS

A high-performance liquid chromatographic (HPLC) assay for determination of sotalol enantiomers in biological fluids was developed to assess the stereoselective disposition of the drug in man. Following extraction at pH 9.0 with a mixture of chloroform isopropanol (3:1, v/v), the organic phase was evaporated to dryness and the residue derivatized with (-)-menthyl chloroformate. Diastereoisomeric derivatives were resolved by HPLC (C-8 column) with fluorescence detection (lambda(ex) = 235 nm and lambda(em) = 300 nm). Retention times of l- and d-sotalol derivatives were 13 and 15 min while that of the internal standard, S-(-)-atenolol, was 12.3 min. The detection limit of each enantiomer was 12.5 ng/ml using 1 ml of plasma or urine. Intra-day and inter-day coefficients of variation were less than 10% for each enantiomer in the range 0.125-2.5 mug/ml in plasma and 0.25-2.5 mug/ml in urine.