DIRECT HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION IN URINE OF THE ENANTIOMERS OF PROPRANOLOL AND ITS MAJOR BASIC METABOLITE 4-HYDROXYPROPRANOLOL

A method is described for quantitation of underivatized enantiomers of propranolol and its major basic metabolite, 4-hydroxypropranolol, in urine samples by high-performance liquid chromatography with fluorescence detection, using a cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase. This method was found to be precise and accurate for the measurement of propranolol and 4-hydroxypropranolol concentrations in urine from pharmacokinetic investigations. This method represents the first assay for direct determination of 4-hydroxypropranolol enantiomers. The ability to easily measure 4-hydroxypropranolol enantiomers is valuable because the stereoselective disposition of propranolol is primarily due to stereoselective metabolism in the pathway responsible for generation of 4-hydroxypropranolol.