In the past decade, more than 100 different cathinone derivatives slopped over entire Europe due to their enormous popularity. Generally, these novel psychoactive substances are easily available via the internet. This fact leads to various social problems, since cathinones are substances with consciousness‐changing effects and are mainly misused for recreational matters by their consumers. Cathinones possess a chiral center including two enantiomeric forms with potentially different pharmacological behavior. This fact makes analytical method development regarding their chiral separation indispensable. In this study, a chiral capillary zone electrophoresis method for the enantioseparation of 61 cathinone and pyrovalerone derivatives was developed by means of four different β‐cyclodextrin derivatives. As chiral selectors, native β‐cyclodextrin as well as three of its derivatives namely acetyl‐β‐cyclodextrin, 2‐hydroxypropyl‐β‐cyclodextrin, and carboxymethyl‐β‐cyclodextrin were used. The cathinone and pyrovalerone derivatives were either purchased in internet stores or seized by police. As a result, overall 58 of 61 studied substances were partially or baseline separated by at least one of the four chiral selectors using 10 mM of β‐cyclodextrin derivative in a 10 mM sodium phosphate buffer (pH 2.5). Furthermore, the method was found to be suitable for simultaneous enantioseparations, for enantiomeric purity checks and to differentiate between positional isomers. Moreover, an intra‐ and an interday validation was performed successfully for each chiral selector to prove the robustness of the method.

Besides the abuse of well‐known illicit drugs, consumers discovered new synthetic compounds with similar effects but minor alterations in their chemical structure. Originally, these so‐called novel psychoactive substances (NPS) have been created to circumvent law of prosecution because of illicit drug abuse. During the past decade, such compounds came up in generations, the most popular compound was a synthetic cathinone derivative named mephedrone. Cathinones are structurally related to amphetamines; to date, more than 120 completely new derivatives have been synthesized and are traded via the Internet. Cathinones possess a chiral center; however, only little is known about the pharmacology of their enantiomers. However, NPS comprise further chiral compound classes such as amphetamine derivatives, ketamines, 2‐(aminopropyl)benzofurans, and phenidines. In continuation of our project, a cheap and easy‐to‐perform chiral capillary zone electrophoresis method for enantioseparation of cathinones presented previously was extended to the aforementioned compound classes. Enantioresolution was achieved by simply adding native β‐cyclodextrin, acetyl‐β‐cyclodextrin, 2‐hydroxypropyl‐β‐cyclodextrin, or carboxymethyl‐β‐cyclodextrin as chiral selector additives to the background electrolyte. Fifty‐one chiral NPS served as analytes mainly purchased from online vendors via the Internet. Using 10 mM of the aforementioned β‐cyclodextrins in a 10 mM sodium phosphate buffer (pH 2.5), overall, 50 of 51 NPS were resolved. However, chiral separation ability of the selectors differed depending on the analyte. Additionally, simultaneous enantioseparations, the determination of enantiomeric migration orders of selected analytes, and a repeatability study were performed successfully. It was proven that all separated NPS were traded as racemic mixtures.

New psychoactive substances (NPS) count as psychoactive substances, which are slightly modified compared to illicit drugs regarding their chemical structure to circumvent law. Compared to classical drugs such as heroin, cocaine, or amphetamine, they show similar psychoactive effects, however, because of their novelty there is few knowledge about their side effects or toxicity. NPS are available as different chemical substance classes, among them chiral novel derivatives of amphetamine, cathinone, and ketamine. Since in most cases no clinical studies are available about the possibly different effects of the two enantiomers, there is a big demand for enantioseparation method development. Besides high-performance separation techniques such as gas chromatography or HPLC, capillary electrophoresis has turned out to be a powerful alternative for chiral separation development. The addition of chiral additives such as cyclodextrins to the background electrolyte often results in successful attempts. The present study compares the chiral separation power of different previously used non-charged ß-cyclodextrins, among them native ß-cyclodextrin as well as some of its derivatives such as acetyl-, and 2-hydroxypropyl-β-cyclodextrin, with the negatively charged derivatives carboxymethyl-, carboxyethyl- and succinyl-β-cyclodextrin by capillary zone electrophoresis. A total of 136 chiral NPS were investigated with these cyclodextrins, 122 of them were resolved in their enantiomers successfully by means of a simple electrolyte composition consisting of 10 mM aqueous sodium hydrogen phosphate buffer, pH 2.5 and 10 mM of the chiral selector. Furthermore, the presented method turned out to be useful to distinguish between positional isomers and examples for both enantiomer order and positional order for seized samples are given.