1. Characterization and identification of eight designer benzodiazepine metabolites by incubation with human liver microsomes and analysis by a triple quadrupole mass spectrometer
- Author
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Maxime Chaslot, Olivier Mathieu, Martine Delage, Nicolas Picard, Souleiman El Balkhi, S. Dulaurent, Franck Saint-Marcoux, Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hydrosciences Montpellier (HSM), and Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Designer benzodiazepines ,Adult ,Male ,Substance-Related Disorders ,Metabolite ,NPS ,Lorazepam ,01 natural sciences ,Pathology and Forensic Medicine ,Designer Drugs ,03 medical and health sciences ,Nifoxipam ,chemistry.chemical_compound ,Benzodiazepines ,0302 clinical medicine ,Tandem Mass Spectrometry ,Human liver microsomes ,medicine ,Clonazolam ,Humans ,030216 legal & forensic medicine ,General unknown screening ,QTRAP ,Chromatography ,Chemistry ,Oxazepam ,010401 analytical chemistry ,Flubromazepam ,Desmethyl ,0104 chemical sciences ,3. Good health ,Triple quadrupole mass spectrometer ,Deschloroetizolam ,New psychoactive substances ,Microsomes, Liver ,Flubromazolam ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,medicine.drug ,Chromatography, Liquid - Abstract
International audience; Designer benzodiazepines (DBZDs) have become of particular importance in the past few years. The metabolite monitoring of DBZD in biological fluids could be of great interest in clinical and forensic toxicology. However, DBZD metabolites are not known or not commercially available. The identification of some DBZD metabolites has been mostly explored by self-administration studies or by in vitro studies followed by high-resolution mass spectrometry. The question arose whether a unit resolution instrument could be efficient enough to allow the identification of DBZD metabolites. In this study, we used an in vitro experiment where eight DBZDs (diclazepam, flubromazepam, etizolam, deschloroetizolam, flubromazolam, nifoxipam, meclonazepam and clonazolam) were incubated with human liver microsomes (HLMs) and metabolite identification was carried out by using a UHPLC coupled to a QTRAP triple quadrupole linear iontrap tandem mass spectrometer system. Post-mortem samples obtained from a real poisoning case, involving deschloroetizolam and diclazepam, were also analysed and discussed. Our study using HLM allowed the identification of 26 metabolites of the 8 DBZDs. These were denitro-, mono- or di-hydroxylated and desmethyl metabolites. In the forensic case, diclazepam was not detected whereas its metabolites (lormetazepam and lorazepam) were present at high concentrations in urine. We also identified hydroxy-deschloroetizolam in urine, while the parent compound was not detected in this matrix. This supports the approach that LC coupled to a simple QTRAP could be used by laboratories to identify other not-known/not-commercialized new psychoactive substance (NPS) metabolites.
- Published
- 2016