Chiral Separation of Cathinone and Amphetamine Derivatives by HPLC/UV Using Sulfated ß‐Cyclodextrin as Chiral Mobile Phase Additive

Abstract

In the last years the identification of new legal and illegal highs has become a huge challenge for the police and prosecution authorities. In an analytical context, only a few analytical methods are available to identify these new substances. Moreover, many of these recreational drugs are chiral and it is supposed that the enantiomers differ in their pharmacological potency. Since nonenantioselective synthesis is easier and cheaper, they are mainly sold as racemic mixtures. The goal of this research work was to develop an inexpensive method for the chiral separation of cathinones and amphetamines. This should help to discover if the substances are sold as racemic mixtures and give further information about their quality as well as their origin. Chiral separation of a set of 6 amphetamine and 25 cathinone derivatives, mainly purchased from various Internet shops, is presented. A LiChrospher 100 RP-18e, 250 x 4 mm, 5 µm served as the stationary phase. The chiral mobile phase consisted of methanol, water, and sulfated ß-cyclodextrin. Measurements were performed under isocratic conditions in reversed phase mode using UV detection. Four model compounds of the two substance classes were used to optimize the mobile phase. Under final conditions (methanol:water 2.5:97.5 + 2% sulfated ß-cyclodextrin) enantiomers of amphetamine and five derivatives were baseline separated within 23 min. In all, 17 cathinones were completely or partially chirally separated. However, as only 3 of 25 cathinones were baseline resolved, the application of this method is limited for cathinone analogs. Additionally, the results were compared with an RP-8e column.

Isolation and structural determination of non-racemic tertiary cathinone derivatives

“…They are normally obtained in a stable protonated solid form, generally assumed to be the chloride salt. These include using HPLC with either a chiral stationary phase [41][42][43][44] or a chiral additive to the eluent, 45 GC following chiral derivatization of the analyte, 30,42,[46][47][48] capillary electrophoresis, [49][50][51][52] and NMR spectroscopy using appropriate chiral auxiliaries. 3 Calculations have predicted the pK a to be in the range of 8.4 to 9.5, suggesting that these compounds remain protonated at physiological pH, and unlike the analogous amphetamine derivatives, it is predicted that the ketone group increases both the planarity of the compound, and the hydrophilicity so lowering their activity with respect to the parent amphetamine, being less likely to cross cell membranes.…”

An overview of recent developments in the analytical detection of new psychoactive substances (NPSs)

“…19 This is potentially problematic as in many instances users are, due to poorly labelled products (see earlier), not in fact aware of the substances they are taking. 43 In 2014 Archer et al 19 analysed urine samples collected from a night club over one weekend. A number of revered groups using a range of chromatographic techniques including high performanceliquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS), with LC-MS methods seemingly the preferred and established technique of choice, have published exhaustively upon the laboratory-based analysis of synthetic cathinones, 3,20-40 phase I and II metabolites 41,42 and more recently, in light of the often nonenantioselective NPS synthesis, chiral separation of racemic mixtures.…”

Regioisomeric and enantiomeric analyses of 24 designer cathinones and phenethylamines using ultra high performance liquid chromatography and capillary electrophoresis with added cyclodextrins

“…HPLC using cyclodextrin (CD) as a chiral additive to the mobile phase has been reported for chiral separation of phenethylamines and cathinones [33,34]; however, these methods…”