Methoxyacetylfentanyl is one of many fentanyl analogs available as new psychoactive substances. It have been encountered in both the European Union and the United States, and existing literature suggest that methoxyacetylfentanyl is around 3- to 5-fold less potent than fentanyl. The aim of the present work was to combine case information with blood concentrations and abundance of urinary metabolites to investigate the importance of these parameters for toxicological interpretation. Quantification of methoxyacetylfentanyl in femoral blood was performed by LC--MS-MS and urinary metabolites were analyzed by LC--QTOF-MS with and without hydrolysis with β-glucuronidase/arylsulfatase. For confirmation of identified metabolites, methoxyacetylfentanyl was incubated with hepatocytes for up to 5 hours and analyzed with the same method as the urine samples. In eleven postmortem cases (27 to 41 years old and including one female) methoxyacetylfentanyl was reported in femoral blood. The cause of death was intoxication by methoxyacetylfentanyl alone or in combination with other drugs in all but one case, where death was attributed to acute complications of an underlying heart disease but with possible contribution from methoxyacetylfentanyl. In total, 27 urinary metabolites were found, including eight glucuronides. Major biotransformations were O-demethylation, dealkylation to form the nor-metabolite, mono- and dihydroxylations of the phenethyl moiety, as well as combinations thereof. The most abundant metabolites in hydrolyzed urine included O-desmethyl-, O-desmethyl-phenethyl-hydroxy-, O-desmethyl-phenethyl-hydroxymethoxy- and nor-methoxyacetylfentanyl. Differences in the abundance of methoxyacetylfentanyl and its major metabolites could be interpreted to indicate fatal intoxications in abstinent or chronic users. We postulate that urinary concentrations of methoxyacetylfentanyl and two metabolites, in combination with the methoxyacetylfentanyl concentration in femoral blood, might be good indicators of the time between administration and death as well as prior use.

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一系列甲氧基乙酰芬太尼相关死亡的情况、尸检结果、血液浓度和代谢

甲氧基乙酰芬太尼是许多可用作新型精神活性物质的芬太尼类似物之一。它已在欧盟和美国遇到，现有文献表明甲氧基乙酰芬太尼的效力比芬太尼低 3 至 5 倍。本工作的目的是将病例信息与血液浓度和尿代谢物的丰度相结合，以研究这些参数对毒理学解释的重要性。股血中甲氧基乙酰芬太尼的定量通过 LC--MS-MS 进行，尿液代谢物通过 LC-QTOF-MS 进行分析，无论是否使用 β-葡萄糖醛酸酶/芳基硫酸酯酶水解。为了确认已鉴定的代谢物，甲氧基乙酰芬太尼与肝细胞孵育长达 5 小时，并使用与尿液样本相同的方法进行分析。据报道，在 11 例死后病例（27 至 41 岁，包括一名女性）中，股血中有甲氧基乙酰芬太尼。死亡原因是单独使用甲氧基乙酰芬太尼或与其他药物合用，但只有一个病例死亡，其中死亡归因于潜在心脏病的急性并发症，但甲氧基乙酰芬太尼可能有贡献。总共发现了 27 种尿液代谢物，其中包括 8 种葡糖苷酸。主要的生物转化是 O-去甲基化、去烷基化形成去甲代谢物、苯乙基部分的单羟基化和二羟基化，以及它们的组合。水解尿液中最丰富的代谢物包括 O-去甲基-、O-去甲基-苯乙基-羟基-、O-去甲基-苯乙基-羟基甲氧基-和去甲氧基乙酰芬太尼。甲氧基乙酰芬太尼及其主要代谢物的丰度差异可以解释为表明戒断或慢性使用者的致命中毒。我们假设尿中甲氧基乙酰芬太尼和两种代谢物的浓度与股血中的甲氧基乙酰芬太尼浓度相结合，可能是给药与死亡之间以及先前使用之间时间的良好指标。