title: Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics.
abstract: The appearance of pyrazolam in Internet shops selling 'research chemicals' in 2012 marked the beginning of designer benzodiazepines being sold as recreational drugs or 'self medication'. With recent changes in national narcotics laws in many countries, where two uncontrolled benzodiazepines (phenazepam and etizolam), which were marketed by pharmaceutical companies in some countries, were scheduled, clandestine laboratories seem to turn to poorly characterized research drug candidates as legal substitutes. Following the appearance of pyrazolam, it comes with no surprise that recently, flubromazepam (7-bromo-5-(2-fluorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one), a second designer benzodiazepine, was offered on the market. In this article, this new compound was characterized using nuclear magnetic resonance, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS/MS) and liquid chromatography quadrupole time-of-flight MS (LC-Q-ToF-MS). Additionally, a study was carried out, in which one of the authors consumed 4 mg of flubromazepam to gain preliminary data on the pharmacokinetic properties and the metabolism of this compound. For this purpose, serum as well as urine samples were collected for up to 31 days post-ingestion and analyzed applying LC-MS/MS and LC-Q-ToF-MS techniques. On the basis of this study, flubromazepam appears to have an extremely long elimination half-life of more than 100 h. One monohydroxylated compound and the debrominated compound could be identified as the predominant metabolites, the first allowing a detection of a consumption for up to 28 days post-ingestion when analyzing urine samples in our case. Additionally, various immunochemical assays were evaluated, showing that the cross-reactivity of the used assay seems not to be sufficient for safe detection of the applied dose in urine samples, bearing the risk that it could be misused in drug-withdrawal settings or in other circumstances requiring regular drug testing. Furthermore, it may be used in drug-facilitated crimes without being detected.
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology Department, University Medical Center Freiburg, Albertstr. 9, 79104, Freiburg, Germany; Hermann Staudinger Graduate School, University of Freiburg, Hebelstr. 27, 79104, Freiburg, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Moosmann
authors.forename: Laura M
authors.initials: LM
authors.lastname: Huppertz
authors.forename: Melanie
authors.initials: M
authors.lastname: Hutter
authors.forename: Armin
authors.initials: A
authors.lastname: Buchwald
authors.forename: Sascha
authors.initials: S
authors.lastname: Ferlaino
authors.forename: Volker
authors.initials: V
authors.lastname: Auwärter
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D002214:Capsules / Q000737:chemistry*; D015198:Designer Drugs / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans
chemical_list: D002214:Capsules; D015198:Designer Drugs; D001569:Benzodiazepines
keywords: LC-MS/MS; benzodiazepines; flubromazepam; immunoassay; serum; urine