STEREOSPECIFIC ASSAY FOR (-)-PROPRANOLOL AND (+)-PROPRANOLOL IN HUMAN AND DOG PLASMA

Abstract

Propranolol [1-isopropylamino-3-(1-Naphthoxy)-2-propanol] is a nonselective .beta.-adrenergic blocking agent used clinically as the racemic mixture. As (-)-propranolol is .apprx. 100 times more potent than its optical antipode, significant differencs in their disposition may be important clinically, especially if affected by disease state. The present technique, for the 1st 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. Derivativation is quantitative (> 98%) from 2-1000 ng/ml; 4-hydroxy and N-deisopropyl 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 2 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.