HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF (S)-PROPRANOLOL AND (R)-PROPRANOLOL IN HUMAN PLASMA AND URINE WITH A CHIRAL BETA-CYCLODEXTRIN-BONDED PHASE

The determination of propranolol enantiomers in microsamples of human plasma and urine by HPLC using a chiral stationary phase is described. After extraction from 200 mu l of plasma or urine with racemic alpren olol as internal standard (I.S.), the enantiomers are separated on a b eta-cyclodextrin column with a polar organic mobile phase and determin ed by fluorescence detection. The retention times of I.S. and proprano lol enantiomers are about 12-13 min and 16-18 min, respectively. Peak resolutions are 1.4 for I.S. and 2.2 for propranolol. The use of alpre nolol as I.S. improves significantly the coefficients of variation (C. V.: 0.6-4.2%). Sensitivity is approximately 1.5 ng/ml per propranolol enantiomer. The assay is applied to pharmacokinetic studies of racemic propranolol in human biological fluids. The (S)-propranolol levels ar e always higher than the (R)-antipode concentrations in plasma and uri ne.