Enantioselective analysis of the methamphetamine precursors ephedrine and pseudoephedrine by capillary electrokinetic chromatography using cyclodextrins as chiral selectors

Abstract

Ephedrine and pseudoephedrine can be used as precursors for the illicit synthesis of stimulant drugs, such as methamphetamine and methcathinone. For this reason, an enantioselective capillary electrokinetic chromatography method was developed for the separation of ephedrine and pseudoephedrine enantiomers. After testing two different charged or chargeable cyclodextrins (β-cyclodextrin sulphate and carboxymethyl-β-cyclodextrin) and a few mixtures as possible chiral selectors, a mixture of 3 mM carboxymethyl-β-cyclodextrin and 3 mM heptakis(2,6-di-O-methyl)-β-cyclodextrin in pH 3.4 acetate buffer was used as the enantioselective background electrolyte and the separation was carried out in an uncoated silica capillary (75 µm internal diameter, 48.6 cm total length, 40.0 cm effective length). Analytical method performance was then evaluated in terms of linearity, precision, selectivity and accuracy with good results. Proof of concept application to mixtures simulating illicit methamphetamine (containing small amounts of ephedrine and pseudoephedrine as possible residual synthesis impurities) provided satisfactory results for the identification and quantitation of the four analyte diastereomers.