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<p>Nitazenes constitute a structurally diverse class of non-fentanyl synthetic opioids that have rapidly emerged in the European illicit drug market since 2019. Bridging analytical, seized drug epidemiology, and interpretative gaps would support meaningful interpretation of nitazene-related deaths. This study presents a fit-for-purpose LC–MS/MS method for the quantitation of six nitazenes, etazene, isotonitazene, <i>N</i>-pyrrolidino isotonitazene, metonitazene, <i>N</i>-pyrrolidino metonitazene, and protonitazene in postmortem blood. The method was applied to analyze 57 nitazene-positive autopsy cases received between December 2020 and December 2024 by the Swedish National Board of Forensic Medicine. During this period, metonitazene (n = 38) and protonitazene (n = 10) were the most encountered nitazenes, with femoral blood concentrations in mono-intoxicated cases ranging from 0.3 to 34&#xa0;ng/g and 1.7 to 4.9&#xa0;ng/g respectively. Complementary <i>in vitro</i> MOR activation studies using AequoScreen® assays demonstrated that these nitazenes possess potencies (0.17–6.0&#xa0;nM) and efficacies comparable to, or exceeding, those of fentanyl. The predominance of metonitazene prompted further investigation into its metabolism and stability profile, where analysis of authentic postmortem cases indicated the presence of three possible metabolites (<i>N</i>-desethyl, acetamido, 5-amino metonitazene) alongside other amino-containing degradation products. Further studies elucidating true metabolites from postmortem or storage-related breakdown products would support interpretation of nitazene exposure in casework. These findings provide an overview of nitazenes in Swedish forensic casework and address a critical gap in region-specific data, underscoring the need for sustained analytical vigilance and proactive toxicovigilance strategies to ensure timely detection and accurate interpretation of nitazene-related mortalities in an evolving drug landscape.</p>

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Fatal intoxications with nitazenes: postmortem findings, toxicology, and in vitro characterization at the μ-opioid receptor of six nitazene analogues

  • 期刊论文

  • 发表日期：

    2026年4月25日

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  • Michael T. Truver,
  • Markus Roman,
  • Munchelou M. Gomonit,
  • Henrik Gréen,
  • Robert Kronstrand,
  • Mattias Persson

摘要

Nitazenes constitute a structurally diverse class of non-fentanyl synthetic opioids that have rapidly emerged in the European illicit drug market since 2019. Bridging analytical, seized drug epidemiology, and interpretative gaps would support meaningful interpretation of nitazene-related deaths. This study presents a fit-for-purpose LC–MS/MS method for the quantitation of six nitazenes, etazene, isotonitazene, N-pyrrolidino isotonitazene, metonitazene, N-pyrrolidino metonitazene, and protonitazene in postmortem blood. The method was applied to analyze 57 nitazene-positive autopsy cases received between December 2020 and December 2024 by the Swedish National Board of Forensic Medicine. During this period, metonitazene (n = 38) and protonitazene (n = 10) were the most encountered nitazenes, with femoral blood concentrations in mono-intoxicated cases ranging from 0.3 to 34 ng/g and 1.7 to 4.9 ng/g respectively. Complementary in vitro MOR activation studies using AequoScreen® assays demonstrated that these nitazenes possess potencies (0.17–6.0 nM) and efficacies comparable to, or exceeding, those of fentanyl. The predominance of metonitazene prompted further investigation into its metabolism and stability profile, where analysis of authentic postmortem cases indicated the presence of three possible metabolites (N-desethyl, acetamido, 5-amino metonitazene) alongside other amino-containing degradation products. Further studies elucidating true metabolites from postmortem or storage-related breakdown products would support interpretation of nitazene exposure in casework. These findings provide an overview of nitazenes in Swedish forensic casework and address a critical gap in region-specific data, underscoring the need for sustained analytical vigilance and proactive toxicovigilance strategies to ensure timely detection and accurate interpretation of nitazene-related mortalities in an evolving drug landscape.