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Characterization of the four designer benzodiazepines clonazolam, deschloroetizolam, flubromazolam, and meclonazepam, and identification of their in vitro metabolites

Forensic Toxicology volume 33, pages 388–395 (2015)Cite this article

Abstract

In 2012, the first designer benzodiazepines were offered in Internet shops as an alternative to prescription-only benzodiazepines. Soon after these compounds were scheduled in different countries, new substances such as clonazolam, deschloroetizolam, flubromazolam, and meclonazepam started to emerge. This article presents the characterization of these four designer benzodiazepines using nuclear magnetic resonance spectroscopy, gas chromatography–electron ionization-mass spectrometry, liquid chromatography–tandem mass spectrometry, liquid chromatography–quadrupole time-of-flight-mass spectrometry, and infrared spectroscopy. The major in vitro phase I metabolites of the substances were investigated using human liver microsomes. At least one monohydroxylated metabolite was identified for each compound. Dihydroxylated metabolites were found for deschloroetizolam and flubromazolam. For clonazolam and meclonazepam, signals at mass-to-charge ratios corresponding to the reduction of the nitro group to an amine were observed. Desalkylations, dehalogenations, or carboxylations were not observed for any of the compounds investigated. Furthermore, for clonazolam and meclonazepam, no metabolites formed by a combination of reduction and mono-/dihydroxylation were detected. This knowledge will help to analyze these drugs in biological samples.

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Acknowledgements

This publication has been produced with the financial support of the Drug Prevention and Information Programme of the European Union (JUST/2011/DPIP/AG/3597), the German Federal Ministry of Health, and the City of Frankfurt/Main.

Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Albertstr.9, 79104, Freiburg, Germany

    Laura M. Huppertz, Florian Franz, Volker Auwärter & Bjoern Moosmann

  2. Institute of Pharmaceutical Sciences, University of Freiburg, Freiburg, Germany

    Philippe Bisel

  3. Hermann Staudinger Graduate School, University of Freiburg, Freiburg, Germany

    Florian Franz

  4. State Office of Criminal Investigation Schleswig-Holstein, Kiel, Germany

    Folker Westphal

Authors
  1. Laura M. Huppertz
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  2. Philippe Bisel
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  3. Folker Westphal
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  4. Florian Franz
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  5. Volker Auwärter
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  6. Bjoern Moosmann
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Corresponding author

Correspondence to Bjoern Moosmann.

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Huppertz, L.M., Bisel, P., Westphal, F. et al. Characterization of the four designer benzodiazepines clonazolam, deschloroetizolam, flubromazolam, and meclonazepam, and identification of their in vitro metabolites. Forensic Toxicol 33, 388–395 (2015). https://doi.org/10.1007/s11419-015-0277-6

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  • DOI: https://doi.org/10.1007/s11419-015-0277-6

Keywords

  • Designer benzodiazepines
  • Clonazolam
  • Deschloroetizolam
  • Flubromazolam
  • Meclonazepam
  • Phase I metabolism