Enantioseparation of Three Synthetic Cathinones: An Evaluation of CHIRALPAK® AD-3 Column Using HPLC

All new designer drugs derived from cathinone, the principal active ingredient present in the leaves of the catha edulis (Khat) plant, have a chiral center at their α-carbon yielding two stereoisomers. It is well known that one of the enantiomers is biologically active, whereas the other may be inactive or pose undesired effect. Owing to the novelty of these compounds, limited data about the pharmacological and toxicological, and consequently about the single enantiomers are available. Analytical methods are therefore required to discriminate between the two enantiomers of a new racemic drug. Three synthetic cathinones namely, mephedrone, N-Ethylpentylone and 4-Cl-alpha-PPP were used as model compounds. The chiral HPLC method is composed of CHIRALPAK® AD-3 column, methanol–ethanol–diethylamine as mobile phase with a flow rate of 0.1 ml/min and UV detection at 254 nm. The effects of different mobile phase ratios on the retention time and resolution were evaluated to achieve baseline separation. Under final conditions (methanol–ethanol–diethylamine [95:5:0.1 v/v]), mephedrone has transformed into a complete separation by increasing the methanol content from 80% to 95%. However, both 4-Cl-alpha-PPP and N-Ethylpentylone were only partially resolved although a remarkable resolution was observed. Nevertheless, the applicability of the developed chiral method could be expanded to a wider range of designer drugs to provide much more precise knowledge.