Characterization of the four designer benzodiazepines clonazolam, deschloroetizolam, flubromazolam, and meclonazepam, and identification of their in vitro metabolites
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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.
KeywordsDesigner benzodiazepines Clonazolam Deschloroetizolam Flubromazolam Meclonazepam Phase I metabolism
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.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 5.Huppertz LM, Kneisel S, Auwärter V, Kempf J (2014) A comprehensive library-based, automated screening procedure for 46 synthetic cannabinoids in serum employing liquid chromatography-quadrupole ion trap mass spectrometry with high-temperature electrospray ionization. J Mass Spectrom 49:117–127PubMedCrossRefGoogle Scholar
- 6.Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl)benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281CrossRefGoogle Scholar
- 14.Abe M, Mikashima H, Moriwaki M, Tahara T (1988) Thieno(triazolo)diazepine compound and medicinal application of the same. Patent WO1988009333A1Google Scholar
- 15.Sternbach LH, Randall LO, Banziger R, Lehr H (1968) Structure–activity relationships in the 1,4-benzodiazepine series. In: Burger A (ed) Drugs affecting the central nervous system, vol 2. Edward Arnold, LondonGoogle Scholar
- 18.Cayman Chemical (2014) Cayman Spectral library. https://www.caymanchem.com/app/template/SpectralLibrary. Accessed December 2014
- 19.Maurer HH, Pfleger K, Weber AA (2011) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites, 4th edn. Wiley-VCH, WeinheimGoogle Scholar