Development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 16 ‘legal high’ cathinone derivatives

doi:10.1016/j.scijus.2013.08.004

Science & Justice

Volume 54, Issue 1, January 2014, Pages 22-31

https://doi.org/10.1016/j.scijus.2013.08.004 Get rights and content

Abstract

The prevalence of so-called ‘legal high’ drugs in forensic science drug casework has increased markedly in recent years. This has given rise to both legal and analytical challenges in the identification of these substances. The requirement for validated, reliable and rapid testing methodologies for these compounds is obvious. This work reports the analysis of sixteen synthesised cathinone derivatives encountered in casework using presumptive testing, thin layer chromatography and gas chromatography–mass spectrometry (GC–MS).

Introduction

The UNODC World Drug Report 2012 [1] describes an increased prevalence of substances marketed or sold as ‘legal highs’ and ‘bath salts’, specifically 4′-methylmethcathinone (4-MMC, Mephedrone) and 3,4-methylenedioxypyrovalerone (MDPV) in all regions but particularly Europe, North America and Oceania. According to the EMCDDA [2], most cathinones appearing on the European illicit drug market are reported to be synthesised outside Europe, with China and, to a lesser extent, India identified as the primary source countries.

The shift to a more widespread and readily-available virtual market for ‘legal high’ drugs on the Internet has significantly altered the pattern of illicit drug trading with regard to the distribution, sales and marketing of these materials [3]. A recent EMCDDA ‘snapshot’ reported that the number of online shops offering ‘legal high’ compounds in January 2012 was 693 in comparison to 314 in January 2011 and 170 in January 2010 [4].

The Internet not only provides information about cathinones and legal high drugs, but also serves as a globalised drug market for the distribution and sales of these novel psychoactive substances (NPS) [3]. The Internet provides a vast array of sources where materials can be advertised from social network websites, online head shops, discussion forums, blogs etc.

This increased illegal use of substituted cathinone compounds has required the development of rapid testing methods for both their identification and quantification. The deficiency of such tests was reported by the UK government Advisory Council on the Misuse of Drugs in its consideration of the analysis of cathinone related compounds [5]. Further laboratory analysis using accurate and reliable methods for thin layer chromatography (TLC) as a fast sample screen followed by identification and quantification of target compounds using for example, gas chromatography–mass spectrometry (GC–MS) is also required. This current work reports presumptive test, thin layer chromatographic and GC–MS data for sixteen cathinone derivatives encountered in casework. Specifically, the GC–MS method provides a general screening method for samples. Additionally the Supplementary information includes the characterization data (¹H NMR, ¹³C NMR and FTIR) for the synthesised compounds prepared and utilised in this study and serves as additional comparative information for laboratories engaged in the routine analysis of these compounds. We have also included GC–MS data for the three most commonly encountered adulterants, namely, benzocaine, lidocaine and procaine and have illustrated that the GC–MS method facilitates separation of these compounds from the target analytes.

Section snippets

Materials and methods

Known provenance samples of all compounds were prepared as detailed below. An example of the reaction scheme is presented for 4′-methylmethcathinone in reaction Scheme 1.

All reagents were of commercial quality (Sigma-Aldrich, Gillingham, UK) and used without further purification. Solvents (Fisher Scientific, Loughborough, UK) were dried, where necessary, using standard procedures. ¹H and ¹³C NMR spectra were acquired on both JEOL AS-400 (JEOL, Tokyo, Japan) and Bruker Avance 400 (Bruker,

Synthesis

Samples of the cathinones (see Table 1) were prepared as their corresponding hydrochloride or hydrobromide salts. The synthesis of the racemic target compounds was achieved using a modification of the previously reported methods [6], [7], [8], [9] from prerequisite (±)-α-bromoketones in 20–86% overall yield, respectively as stable, colourless to off-white powders after recrystallization from acetone. To ensure the authenticity of the materials utilised in this study the synthesised samples were

Conclusions

We have presented the results of analysis of sixteen substituted cathinone samples commonly encountered as ‘legal high’ drugs in casework. All analyses were undertaken on known provenance samples prepared in house. The Zimmerman presumptive test provided a simple and rapid test for these materials and some separation of the compounds was possible using conventional thin layer chromatographic analysis.

The developed method for GC–MS analysis provides a screening method which facilitates the

Acknowledgements

The authors wish to thank Mr Craig Irving (Department of Pure & Applied Chemistry) and Mr Paul Warren (Manchester Metropolitan University) for carrying out the NMR analysis of the compounds utilised in this study and the University of Strathclyde for funding the project.

References (12)

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(2012)
European Monitoring Centre for Drugs, Drug Addiction (EMCDDA)
Annual Report 2012
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I. Vardakou et al.
Drugs for youth via Internet and the example of mephedrone
Toxicol. Lett.
(2011)
European Monitoring Centre for Drugs, Drug Addiction (EMCDDA)
Briefing paper: online sales of new psychoactive substances/‘legal highs’: summary of results from the 2011 multilingual snapshots
Consideration of the cathinones, Advisory Council on the Misuse of Drugs, UK Home Office
O.I.G. Khreit et al.
Elucidation of the phase I and phase II metabolic pathways of (±)-4′-methylmethcathinone (4-MMC) and (±)-4′-(trifluoromethyl)methcathinone (4-TFMMC) in rat liver hepatocytes using LC–MS and LC–MS²
J. Pharm. Biomed. Anal.
(2013)

There are more references available in the full text version of this article.

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View full text

Development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 16 ‘legal high’ cathinone derivatives

Abstract

Introduction

Section snippets

Materials and methods

Synthesis

Conclusions

Acknowledgements

UNODC World Drug Report 2012

Annual Report 2012

Drugs for youth via Internet and the example of mephedrone

Toxicol. Lett.

Briefing paper: online sales of new psychoactive substances/‘legal highs’: summary of results from the 2011 multilingual snapshots

Consideration of the cathinones, Advisory Council on the Misuse of Drugs, UK Home Office

Elucidation of the phase I and phase II metabolic pathways of (±)-4′-methylmethcathinone (4-MMC) and (±)-4′-(trifluoromethyl)methcathinone (4-TFMMC) in rat liver hepatocytes using LC–MS and LC–MS2

J. Pharm. Biomed. Anal.

Elucidation of the phase I and phase II metabolic pathways of (±)-4′-methylmethcathinone (4-MMC) and (±)-4′-(trifluoromethyl)methcathinone (4-TFMMC) in rat liver hepatocytes using LC–MS and LC–MS²