Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORD

Besides the well-known hallucinogenic ketamine, various novel ketamine derivatives are available on the illicit drug market, sold as designer drugs. Minor chemical changes to the parent compound aim to circumvent existing narcotic drug laws while mimicking the effects of the original substance. Keta...

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Main Authors: Elisabeth Seibert, Eva-Maria Hubner, Martin G. Schmid
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Separations
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Online Access:https://www.mdpi.com/2297-8739/12/2/44
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author Elisabeth Seibert
Eva-Maria Hubner
Martin G. Schmid
author_facet Elisabeth Seibert
Eva-Maria Hubner
Martin G. Schmid
author_sort Elisabeth Seibert
collection DOAJ
description Besides the well-known hallucinogenic ketamine, various novel ketamine derivatives are available on the illicit drug market, sold as designer drugs. Minor chemical changes to the parent compound aim to circumvent existing narcotic drug laws while mimicking the effects of the original substance. Ketamine and some of its derivatives possess a chiral centre and therefore exist as two enantiomers. While differences in the effects of S- and R-ketamine are well studied, this is not the case for ketamine derivatives. Therefore, the development and adaptation of suitable enantioseparation methods for those compounds is important to face the problems of the constantly changing drug market. In this study, different chiral separation methods for capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) were tested on 11 ketamine derivatives. Some of them were enantioseparated for the first time due to their novelty. All compounds were at least partially separated on both instruments. HPLC separations were conducted using four different polysaccharide-based chiral stationary phases. Furthermore, an optical rotation detector coupled to the HPLC enabled the determination of the enantiomer elution order. In CE analysis, enantioseparation was achieved using 2% (<i>w</i>/<i>v</i>) acetyl-β-cyclodextrin or carboxymethyl- β-cyclodextrin in 10 mM di-sodium hydrogen phosphate as the background electrolyte in capillary electrophoresis.
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spelling doaj-art-6468d7c6c54a4dca8a69c7ce22ed1f512025-08-20T02:03:32ZengMDPI AGSeparations2297-87392025-02-011224410.3390/separations12020044Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORDElisabeth Seibert0Eva-Maria Hubner1Martin G. Schmid2Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, 8010 Graz, AustriaInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, 8010 Graz, AustriaInstitute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, 8010 Graz, AustriaBesides the well-known hallucinogenic ketamine, various novel ketamine derivatives are available on the illicit drug market, sold as designer drugs. Minor chemical changes to the parent compound aim to circumvent existing narcotic drug laws while mimicking the effects of the original substance. Ketamine and some of its derivatives possess a chiral centre and therefore exist as two enantiomers. While differences in the effects of S- and R-ketamine are well studied, this is not the case for ketamine derivatives. Therefore, the development and adaptation of suitable enantioseparation methods for those compounds is important to face the problems of the constantly changing drug market. In this study, different chiral separation methods for capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC) were tested on 11 ketamine derivatives. Some of them were enantioseparated for the first time due to their novelty. All compounds were at least partially separated on both instruments. HPLC separations were conducted using four different polysaccharide-based chiral stationary phases. Furthermore, an optical rotation detector coupled to the HPLC enabled the determination of the enantiomer elution order. In CE analysis, enantioseparation was achieved using 2% (<i>w</i>/<i>v</i>) acetyl-β-cyclodextrin or carboxymethyl- β-cyclodextrin in 10 mM di-sodium hydrogen phosphate as the background electrolyte in capillary electrophoresis.https://www.mdpi.com/2297-8739/12/2/44ketamine derivativesnew psychoactive substancesoptical rotation detectioncyclodextrincapillary electrophoresispolysaccharide-based CSPs
spellingShingle Elisabeth Seibert
Eva-Maria Hubner
Martin G. Schmid
Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORD
Separations
ketamine derivatives
new psychoactive substances
optical rotation detection
cyclodextrin
capillary electrophoresis
polysaccharide-based CSPs
title Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORD
title_full Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORD
title_fullStr Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORD
title_full_unstemmed Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORD
title_short Chiral Separation and Determination of Enantiomer Elution Order of Novel Ketamine Derivatives Using CE-UV and HPLC-UV-ORD
title_sort chiral separation and determination of enantiomer elution order of novel ketamine derivatives using ce uv and hplc uv ord
topic ketamine derivatives
new psychoactive substances
optical rotation detection
cyclodextrin
capillary electrophoresis
polysaccharide-based CSPs
url https://www.mdpi.com/2297-8739/12/2/44
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AT evamariahubner chiralseparationanddeterminationofenantiomerelutionorderofnovelketaminederivativesusingceuvandhplcuvord
AT martingschmid chiralseparationanddeterminationofenantiomerelutionorderofnovelketaminederivativesusingceuvandhplcuvord