DIMEC, Department of Medical and Surgical Sciences, University of Bologna, 40126, Bologna, Italy.
Institute of Forensic Medicine, Medical Center-University of Freiburg, 79104, Freiburg, Germany.
Forensic Toxicol. 2022 Jan;40(1):180-188. doi: 10.1007/s11419-021-00591-w. Epub 2021 Aug 11.
Designer benzodiazepines (DBZDs) increasingly emerged on the novel psychoactive substance (NPS) market in the last few years. They are usually sold as readily available alternatives to prescription benzodiazepines (BZDs) or added to counterfeit medicines. BZDs are generally considered relatively safe drugs due to the low risk of serious acute adverse effects in mono-intoxication, though e.g., alprazolam seems to display an elevated risk of respiratory depression. Here we report on a fatal intoxication involving the novel DBZD flualprazolam.
A complete postmortem examination was performed. General unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassay, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. The standard addition method was employed to quantify flualprazolam in postmortem blood and tissues. Finally, a toxicological significance score (TSS) was assigned.
Flualprazolam was detected in heart serum (25.4 ng/mL) and peripheral blood (21.9 ng/mL) as well as in urine, stomach contents, brain, liver and kidney (65.2-323 ng/g). The cause of death was deemed as central nervous system (CNS) and respiratory depression with agonal aspiration of stomach contents, in the setting of a multiple drug intake. Given the concentration levels of the co-consumed CNS depressants, the contribution of flualprazolam to the death was considered likely (TSS of 3).
Our results support that highly potent DBZDs like flualprazolam carry an elevated risk for unintended toxicity, especially in association with other CNS depressants. A multidisciplinary evaluation of fatalities remains mandatory, especially when pharmacological/toxicological data on intoxicating compounds are lacking. To our knowledge this is the first report of flualprazolam concentrations in solid tissues in human.
在过去几年中，新型精神活性物质（NPS）市场上越来越多地出现了设计苯二氮䓬类药物（DBZD）。它们通常被作为现成的处方苯二氮䓬类药物（BZD）替代品销售，或添加到假药中。由于单中毒时严重急性不良反应的风险较低，BZD 通常被认为是相对安全的药物，尽管例如阿普唑仑似乎显示出呼吸抑制的风险升高。在这里，我们报告了一起涉及新型 DBZD 氟拉佐仑的致命中毒事件。
进行了全面的尸检。通过免疫测定、气相色谱-质谱联用和液相色谱-质谱联用，对死后样本进行了一般未知筛查和滥用药物分析。采用标准加入法对死后血液和组织中的氟拉佐仑进行定量。最后，分配了毒性意义评分（TSS）。
在心脏血清（25.4ng/mL）和外周血（21.9ng/mL）以及尿液、胃内容物、大脑、肝脏和肾脏（65.2-323ng/g）中均检测到氟拉佐仑。死因被认为是中枢神经系统（CNS）和呼吸抑制，伴有胃内容物的濒死性吸入，在多种药物摄入的情况下。鉴于共消耗的 CNS 抑制剂的浓度水平，认为氟拉佐仑对死亡的贡献可能（TSS 为 3）。
我们的结果支持像氟拉佐仑这样的高效力 DBZD 类药物具有意外毒性的风险增加，尤其是与其他 CNS 抑制剂一起使用时。对致命事件进行多学科评估仍然是强制性的，特别是在缺乏中毒化合物的药理学/毒理学数据的情况下。据我们所知，这是首例报告氟拉佐仑在人体固体组织中的浓度。
