CHIRAL HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY METHODOLOGY FOR QUALITY-CONTROL MONITORING OF DEXFENFLURAMINE

The objective of this study was to measure the concentration of d-fenfluramine . HCl (the desired product) and l-fenfluramine . HCl (enantiomeric impurity), in the final pharmaceutical product, in the possible presence of its isomeric variants. Sensitivity, stability and specificity were enhanced by derivatizing the analytes with 3,5-dinitrophenylisocyanate utilizing a Pirkle chiral recognition approach. Analysis of the calibration curve data and quality assurance samples showed an overall inter-assay precision of 1.78 and 2.52%, for d-fenfluramine . HCl and l-fenfluramine, with an overall intra-assay precision of 4.75 and 3.67%, respectively. The minimum quantitation limit was 50 ng/ml, having a minimum signal-to-noise ratio of 10, with relative standard deviations of 2.39 and 3.62% for d-fenfluramine and l-fenfluramine. The method is capable of accurately and consistently determining as low as 0.01% l-fenfluramine in the d-fenfluramine final pharmaceutical product.