title: Flubromazolam - Basic pharmacokinetic evaluation of a highly potent designer benzodiazepine.
abstract: Since their first appearance on the Internet in 2012, designer benzodiazepines established as an additional, quickly growing compound class among new psychoactive substances. Data regarding pharmacokinetic parameters, metabolism, and detectability for new compounds are limited or often not available. One of these compounds, flubromazolam (8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine), the triazolo-analogue of flubromazepam, has been offered on the Internet from 2014 on. The purpose of the present study was to assess the period of detectability in biological samples along with preliminary basic pharmacokinetic parameters of the designer benzodiazepine flubromazolam. To investigate these, one of the authors ingested a capsule containing 0.5 mg of the drug. Metabolism studies and suitability tests for the detection with immunochemical assays were performed with the samples obtained from the self-experiment and five authentic case samples. Flubromazolam and its mono-hydroxylated metabolite were detectable by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in urine for up to 6.5 and 8 days, respectively (lower limit of quantification (LLOQ) flubromazolam: 0.1 ng/mL). Peak serum concentrations were as low as 8 ng/mL (8 h post ingestion). Glucuronides were also detected. The terminal elimination half-life could be estimated in the range of 10-20 h. Immunochemical assays yielded negative results for serum samples and positive results for urine samples for up to five days post ingestion. The presented data demonstrate the detectability of a single uptake of 0.5 mg of flubromazolam in hair samples collected two weeks after drug uptake by LC-MS3(cmax0.6 pg/mg; LOD 0.01 pg/mg). The detected metabolites were in good agreement with those described in other studies. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology Department, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Huppertz
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology Department, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Moosmann
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology Department, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
authors.forename: Volker
authors.identifier: http://orcid.org/0000-0002-1883-2804
authors.initials: V
authors.lastname: Auwärter
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D015198:Designer Drugs / Q000032:analysis / Q000493:pharmacokinetics*; D006197:Hair / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D013287:Illicit Drugs / Q000032:analysis / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D015813:Substance Abuse Detection / Q000379:methods* / Q000592:standards
chemical_list: D015198:Designer Drugs; D013287:Illicit Drugs; D001569:Benzodiazepines; C000628386:flubromazolam
keywords: LC-MS/MS; QToF analysis; designer benzodiazepines; in vitro and in vivo metabolism; legal highs