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Forensic Toxicology

, Volume 33, Issue 2, pp 388–395 | Cite as

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

  • Laura M. Huppertz
  • Philippe Bisel
  • Folker Westphal
  • Florian Franz
  • Volker Auwärter
  • Bjoern Moosmann
Short Communication

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.

Keywords

Designer benzodiazepines Clonazolam Deschloroetizolam Flubromazolam Meclonazepam Phase I metabolism 

Notes

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.

Supplementary material

11419_2015_277_MOESM1_ESM.docx (1.5 mb)
Supplementary material 1 (docx 1577 kb)

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Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2015

Authors and Affiliations

  • Laura M. Huppertz
    • 1
  • Philippe Bisel
    • 2
  • Folker Westphal
    • 4
  • Florian Franz
    • 1
    • 3
  • Volker Auwärter
    • 1
  • Bjoern Moosmann
    • 1
  1. 1.Institute of Forensic Medicine, Forensic ToxicologyMedical Center - University of FreiburgFreiburgGermany
  2. 2.Institute of Pharmaceutical SciencesUniversity of FreiburgFreiburgGermany
  3. 3.Hermann Staudinger Graduate SchoolUniversity of FreiburgFreiburgGermany
  4. 4.State Office of Criminal Investigation Schleswig-HolsteinKielGermany

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