Ameline Alice, Gheddar Laurie, Pichini Simona, Stove Christophe, Aknouche Frédéric, Maruejouls Christophe, Raul Jean-Sébastien, Kintz Pascal
Institut de Médecine Légale, 11 rue Humann, 67085 Strasbourg, France.
Institut de Médecine Légale, 11 rue Humann, 67085 Strasbourg, France.
Clin Chim Acta. 2024 Jul 15;561:119764. doi: 10.1016/j.cca.2024.119764. Epub 2024 Jun 4.
Protonitazene, or N,N-diethyl-5-nitro-2-[(4-propoxyphenyl)methyl]-1H-benzimidazole-1-ethanamine, is a novel synthetic opioid, which belongs to the nitazene family. Over the last four years, nitazenes have re-emerged on the new psychoactive substances market and have been reported in several fatal intoxication cases. The metabolism of several nitazene analogues have already been studied, but to date, no data exists regarding protonitazene. The aim of the study was the detection of protonitazene and its metabolites in authentic human urine collected in two fatal intoxication cases, comparing the data after in vitro incubation with human liver microsomes, and subsequent analysis by ultra-performance liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-high-resolution mass spectrometry. Protonitazene metabolites, including N-desethyl-protonitazene, 5-amino-protonitazene and 4-hydroxy-nitazene, were characterized in vitro and were identified in the urine of both cases. The ratios between metabolites and parent protonitazene, higher than 1, were calculated to estimate the proportionality of metabolites. The results suggest that testing protonitazene metabolites should increase the window detection of exposure to protonitazene.
普罗托那嗪，即N,N -二乙基-5-硝基-2-[(4-丙氧基苯基)甲基]-1H-苯并咪唑-1-乙胺，是一种新型合成阿片类药物，属于硝嗪类。在过去四年中，硝嗪类药物在新型精神活性物质市场上再度出现，并在几起致命中毒案件中被报道。已经对几种硝嗪类似物的代谢情况进行了研究，但迄今为止，尚无关于普罗托那嗪的相关数据。本研究的目的是在两起致命中毒案件中收集的真实人类尿液中检测普罗托那嗪及其代谢物，将体外与人肝微粒体孵育后的结果进行比较，并随后通过超高效液相色谱-串联质谱法和超高效液相色谱-高分辨率质谱法进行分析。普罗托那嗪的代谢物，包括N-去乙基普罗托那嗪、5-氨基普罗托那嗪和4-羟基硝嗪，在体外得到了表征，并在两起案件的尿液中均被鉴定出来。计算代谢物与母体普罗托那嗪之间高于1的比率，以估计代谢物的比例关系。结果表明，检测普罗托那嗪代谢物应能扩大普罗托那嗪暴露的检测窗口期。
