NEW CHIRAL HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHODOLOGY USED FOR THE PHARMACOKINETIC EVALUATION OF DEXFENFLURAMINE

A new chiral high-performance liquid chromatographic (HPLC) method uti lizing ultraviolet (UV) detection has been developed for determining p lasma and urinary concentrations of d-fenfluramine and its major metab olite d-norfenfluramine, while being able to determine the possible pr esence of l-fenfluramine after oral administration of enantiopure d-fe nfluramine hydrochloride. Sensitivity, stability, and specificity were enhanced by derivatizing the extracted analytes with 3,5-dinitropheny lisocyanate while utilizing a Pirkle-type chiral recognition approach. In vitro and in vivo statistical data are analogous. Overall plasma i nter-assay precision was less than 7% with a minimum quantitation limi t of 10 ng/ml. Overall urine inter-assay precision was also less than 7% with a minimum quantitation limit of 25 ng/ml.