Flubromazolam – Basic pharmacokinetic evaluation of a highly potent designer benzodiazepine. Issue 1 (19th May 2017)

• Record Type: Journal Article
• Authors: Huppertz, Laura M.; Moosmann, Bjoern; Auwärter, Volker
• Is Part Of: Drug testing and analysis. Volume 10:Issue 1(2018)
• Page Start: 206
• Page End: 211
• Publication Date: 2017-05-19
• Subjects: designer benzodiazepines -- legal highs -- LC–MS/MS -- in vitro and in vivo metabolism -- QToF analysis; Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.2203
• Languages: English
• ISSNs: 1942-7603

Abstract

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‐4 H ‐[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–MS 3 (cmax 0.6 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. Abstract : Designer benzodiazepines are a quickly growing class of compounds among new psychoactive substances. We report on the period of detectability in biological samples and present basic pharmacokinetic data of the highly potent, rather long‐acting designer benzodiazepine flubromazolam, a compound which might well be used in drug facilitated crimes.