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致命性中毒,涉及苯丙胺、氯硝法宗(一种苯二氮䓬前体药物)以及氟乙替嗪(一种新型合成阿片类药物)。

Fatal intoxication involving amphetamine, clonazafone, a benzodiazepine prodrug, and fluoro-etonitazene, a new synthetic opioid.

作者信息

Malzacher Jonas, Pulver Benedikt, Heller Nicolas, Brockbals Lana, Bolliger Stephan A, Kraemer Thomas, Steuer Andrea E, Poetzsch Sandra N

机构信息

Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, Zurich, 8057, Switzerland.

Institute of Legal Medicine, University Hospital Freiburg, Freiburg, Germany.

出版信息

Int J Legal Med. 2025 Oct 20. doi: 10.1007/s00414-025-03627-7.

Abstract

Intoxication cases involving new psychoactive substances (NPS) are known to provide various challenges for forensic toxicological case interpretation, starting with the identification of previously unknown substances. Furthermore, the pharmacological characteristics of these substances, including potency and metabolic processes, remain largely unstudied. In this particular medico-legal case, a 20-year-old man consumed clonazafone and fluoro-etonitazene, which were examined in blood by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, a urine screening was conducted using LC-high-resolution mass spectrometry (HRMS) to investigate the metabolism of these substances, particularly clonazafone. Clonazafone was (semi-)quantified in urine (39 ng/mL), muscle tissue (3.0 ng/g), and stomach content (76'000 ng/mL), but could not be detected in peripheral blood, heart blood, and vitreous humor (lower limit of quantification: 0.1 ng/mL). Additionally, clonazepam (1.5 ng/mL) and its metabolite 7-amino-clonazepam (140 ng/mL), as well as amphetamine (110 ng/mL) and the designer-opioid fluoro-etonitazene (3.3 ng/mL) were found in blood. Within the HR screening, desglycylclonazafone, the intermediate of clonazafone that can be further converted into clonazepam, was detected in the stomach content and urine. Screening in urine has also revealed several metabolites of clonazafone. The cause of death was assumed to be a mixed drug intoxication with fluoro-etonitazene, clonazepam, and amphetamine.

摘要

涉及新型精神活性物质(NPS)的中毒案例给法医毒理学案例解读带来了各种挑战,首先是要鉴定此前未知的物质。此外,这些物质的药理学特性,包括效力和代谢过程,在很大程度上仍未得到研究。在这起特定的法医学案例中,一名20岁男子摄入了氯硝法宗和氟乙替唑仑,通过靶向液相色谱 - 串联质谱法(LC-MS/MS)对其血液进行了检测。此外,还使用液相色谱 - 高分辨率质谱法(HRMS)进行了尿液筛查,以研究这些物质的代谢情况,尤其是氯硝法宗。氯硝法宗在尿液(39纳克/毫升)、肌肉组织(3.0纳克/克)和胃内容物(76000纳克/毫升)中被(半)定量,但在外周血、心脏血液和玻璃体液中未检测到(定量下限:0.1纳克/毫升)。此外,在血液中还发现了氯硝西泮(1.5纳克/毫升)及其代谢物7-氨基氯硝西泮(140纳克/毫升),以及苯丙胺(110纳克/毫升)和合成阿片类物质氟乙替唑仑(3.3纳克/毫升)。在高分辨率筛查中,在胃内容物和尿液中检测到了氯硝法宗的中间体去甘氨氯硝法宗,它可进一步转化为氯硝西泮。尿液筛查还揭示了氯硝法宗的几种代谢物。死亡原因被认为是氟乙替唑仑、氯硝西泮和苯丙胺混合药物中毒。

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