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在法国一个海外省首次出现关于使用质子氮杂环庚三烯致命风险的证据:约5例尸检病例。

First evidence in an oversea French department of the deadly risk of protonitazene use: about 5 post mortem cases.

作者信息

Maruejouls Christophe, Ameline Alice, Gheddar Laurie, Mazoyer Cédric, Teston Kati, Aknouche Frédéric, Kintz Pascal

机构信息

Laboratoire SYNLAB Réunion, 19 ter rue Balbolia, Saint-Paul, 97460, France.

Institut de médecine légale, 11 rue Humann, Strasbourg, 67000, France.

出版信息

Int J Legal Med. 2025 Jan;139(1):87-93. doi: 10.1007/s00414-024-03309-w. Epub 2024 Aug 22.

DOI:10.1007/s00414-024-03309-w
PMID:39168895
Abstract

Protonitazene is a synthetic benzoimidazole opioid of the nitazenes class, developed in the 1950s as an effective analgesic, but never released in the market due to severe side effects and major risk of dependence. The laboratory was involved in the determination of the cause of death for 5 subjects deceased in a French department of the Indian Ocean. The 5 victims were male, aged between 20 and 35 years. The first 2 victims were found dead in their prison cell and the 3 other victims were found dead in a squat. Therefore, we have developed and validated a specific procedure to identify and quantify the drug in post mortem specimens using LC-MS/MS. The procedure involves extraction of 0.5 mL fluid at pH 9.5 with a mixture of organic solvents in presence of 20 ng fentanyl-d used as internal standard. Linearity of the method was verified from 0.1 to 20 ng/mL in both whole blood and urine (r = 0.9983 and 0.9993, respectively). The limit of detection was estimated at 0.05 ng/mL in each matrix. Protonitazene was identified at < LOQ to 0.8 ng/mL, 0.4 to 2.9 ng/mL and 3.0 to 8.0 ng/mL in femoral blood, urine and bile, respectively. Post mortem concentrations were very low, which is consistent with reported high toxicity of protonitazene. As nitazenes represent a growing threat to public health in various parts of the world, this method seems to be a good response to the challenges posed by the identification of this class of substances.

摘要

普罗托氮烯是一种合成的苯并咪唑类阿片类药物,属于氮烯类,于20世纪50年代开发用作有效的镇痛药,但由于严重的副作用和主要的成瘾风险从未投放市场。该实验室参与了对印度洋某法国属地5名死者死因的鉴定。5名受害者均为男性,年龄在20至35岁之间。前两名受害者被发现死于监狱牢房,另外三名受害者被发现死于一个简易住所。因此,我们开发并验证了一种使用液相色谱-串联质谱法(LC-MS/MS)在死后标本中鉴定和定量该药物的特定程序。该程序包括在pH 9.5的条件下,用有机溶剂混合物在20 ng芬太尼-d作为内标物的存在下提取0.5 mL液体。该方法在全血和尿液中的线性范围为0.1至20 ng/mL(r分别为0.9983和0.9993)。每个基质中的检测限估计为0.05 ng/mL。在股动脉血、尿液和胆汁中分别鉴定出普罗托氮烯的含量低于定量限至0.8 ng/mL、0.4至2.9 ng/mL和3.0至8.0 ng/mL。死后浓度非常低,这与报道的普罗托氮烯的高毒性一致。由于氮烯类药物对世界各地的公共卫生构成越来越大的威胁,该方法似乎是应对鉴定这类物质所带来挑战的良好对策。

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Basic Clin Pharmacol Toxicol. 2025 Aug;137(2):e70078. doi: 10.1111/bcpt.70078.

本文引用的文献

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Clin Chim Acta. 2024 Jul 15;561:119764. doi: 10.1016/j.cca.2024.119764. Epub 2024 Jun 4.
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Wastewater-based monitoring of the nitazene analogues: First detection of protonitazene in wastewater.基于污水的硝甲西泮类似物监测:首次在污水中检测到普罗硝西泮。
Sci Total Environ. 2024 Apr 10;920:170781. doi: 10.1016/j.scitotenv.2024.170781. Epub 2024 Feb 13.
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High-throughput quantification of emerging "nitazene" benzimidazole opioid analogs by microextraction and UHPLC-MS-MS.
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J Anal Toxicol. 2023 Dec 12;47(9):787-796. doi: 10.1093/jat/bkad071.
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