Kronstrand Robert, Roman Markus, Johansson Anna, Wu Xiongyu, Green Henrik, Truver Michael T
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, Linköping 587 58, Sweden.
Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 581 83, Sweden.
J Anal Toxicol. 2023 Sep 15;47(7):640-643. doi: 10.1093/jat/bkad041.
Rilmazafone is a pro-drug that can be prescribed in Japan to treat insomnia. Rilmazafone metabolizes into active compounds by a ring closure resulting in a triazolo benzodiazepine structure similar to alprazolam. In mid-2022, the National Board of Forensic Medicine in Sweden were requested to investigate two separate deaths with the suspected use of pagoclone. Packages labeled "Pagoclone" were found at each scene that was suspected to contain rilmazafone based on website information. During screening by high resolution mass spectrometry, rilmazafone metabolites were presumptively identified. Due to the lack of reference material for the active metabolites, the metabolites were synthesized in house and quantification of the compounds identified in the two autopsy cases was prompted. In Case 1, femoral blood concentrations of 7.9, 65 and 170 ng/g of the metabolites rilmazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included the medications haloperidol, alimemazine, fluoxetine, olanzapine and acetaminophen. In Case 2, femoral blood concentrations of 1.7, 1.4 and 70 ng/g of rimazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included loperamide, alimemazine and pregabalin. The intake of rilmazafone was determined as the cause of death in Case 1 and contributed in the Case 2.
瑞马唑仑是一种前体药物，在日本可用于治疗失眠。瑞马唑仑通过闭环代谢为活性化合物，形成一种与阿普唑仑类似的三唑并苯二氮䓬结构。2022年年中，瑞典国家法医学委员会被要求对两起分别疑似使用帕戈克隆的死亡事件展开调查。在每个疑似现场都发现了标有“帕戈克隆”的包装，根据网站信息怀疑其中含有瑞马唑仑。在通过高分辨率质谱进行筛查期间，初步鉴定出了瑞马唑仑的代谢物。由于缺乏活性代谢物的参考物质，于是在内部合成了这些代谢物，并促使对两起尸检案例中鉴定出的化合物进行定量分析。在案例1中，分别检测到股血中代谢物瑞马唑仑、N-去甲基瑞马唑仑和二去甲基瑞马唑仑的浓度为7.9、65和170纳克/克。其他毒理学发现包括药物氟哌啶醇、阿利马嗪、氟西汀、奥氮平和对乙酰氨基酚。在案例2中，分别检测到股血中瑞马唑仑、N-去甲基瑞马唑仑和二去甲基瑞马唑仑的浓度为1.7、1.4和70纳克/克。其他毒理学发现包括洛哌丁胺、阿利马嗪和普瑞巴林。案例1中确定死亡原因是摄入了瑞马唑仑，案例2中瑞马唑仑是促成死亡的因素。
