Abstract

Propranolol is a nonselective beta adrenergic blocking agent used clinically as the racemic mixture. Since (-)-propranolol is about 100 times more potent than its optical antipode, significant differences in their disposition may be important clinically, especially if affected by disease state. The present technique, for the first time, allows for the quantitation of both propranolol enantiomers after administration of the racemic mixture in man and dogs. Enantiomers are reacted with synthetically prepared and optically pure N-trifluoroacetyl-(-)-prolyl chloride, followed by high-performance liquid chromatographic separation of the diastereoisomers using fluorescence detection. Derivatization is quantitative (> 98%) from 2 to 1000 ng/ml; 4-hydroxy and N-desisopropyl propranolol, basic metabolites, do not interfere with the assay. (-)-Propranolol and (+)-propranolol and their corresponding glucuronide concentrations were determined in an angina patient taking 800 mg of propranolol daily and in two dogs given a single oral 80 mg dose. The ratio of the area under the plasma concentration-time curves for (-):(+)-propranolol, and for (-):(+)-propranolol glucuronide were 1.4 and 3.4, respectively, in man, and averaged 0.5, and 3.1, respectively, in dogs.