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.
J Mass Spectrom. 2013 Nov;48(11):1150-9. doi: 10.1002/jms.3279.
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.
2012 年，互联网商店开始销售吡唑仑，标志着苯二氮䓬类药物作为消遣性药物或“自我用药”开始销售。随着许多国家最近对国家麻醉品法进行了修改，两种不受管制的苯二氮䓬类药物（苯甲二氮䓬和依替唑仑）被列入附表，秘密实验室似乎将不受管制的实验室转向了特征不明确的研究药物候选物，以作为合法替代品。继吡唑仑之后，最近又出现了第二种苯二氮䓬类药物氟苯西泮（7-溴-5-（2-氟苯基）-1,3-二氢-2H-1,4-苯并二氮䓬-2-酮），这并不奇怪。在本文中，使用核磁共振、气相色谱-质谱联用（GC-MS）、液相色谱-质谱联用（LC-MS/MS）和液相色谱-四极杆飞行时间质谱联用（LC-Q-ToF-MS）对这种新化合物进行了表征。此外，还进行了一项研究，其中一位作者服用了 4 毫克氟苯西泮，以获得关于该化合物药代动力学特性和代谢的初步数据。为此，在摄入后长达 31 天内收集血清和尿液样本，并应用 LC-MS/MS 和 LC-Q-ToF-MS 技术进行分析。基于这项研究，氟苯西泮的消除半衰期似乎超过 100 小时。可以鉴定出一种单羟基化化合物和去溴化合物为主要代谢物，在我们的案例中，当分析尿液样本时，第一种代谢物可以在摄入后 28 天内被检测到。此外，还评估了各种免疫化学检测方法，结果表明，所用检测方法的交叉反应性似乎不足以在尿液样本中安全检测到应用剂量，存在被滥用于药物戒断环境或其他需要定期药物检测的环境的风险。此外，它可能在没有被检测到的情况下用于药物辅助犯罪。
