Direct high-performance liquid chromatography resolution on a chiral column of dexfenfluramine and its impurities, in bulk raw drug and pharmaceutical formulations

High-performance liquid chromatography (HPLC) was employed for the determination of dexfenfluramine together with the impurities L-fenfluramine (enantiomeric impurity), ortho-(D,L)-fenfluramine and para-(D,L)-fenfluramine in bulk powder and pharmaceutical formulations. The separation of the enantiomers was accomplished, without any derivatization, on a chiral column containing cellulose carbamate (Chiralcel OF) coupled with an achiral column. The effect of diethylamine and 2-propanol, added to the mobile phase was studied. The HPLC method gave good performances, allowing determination of the enantiomeric purity of dexfenfluramine together with the related impurities ortho- and para-(D,L)fenfluramine. The method is capable of determining a minimum limit of 0.5% of L-isomer in commercial samples containing dexfenfluramine.