Clinical toxicology (Philadelphia, Pa.) · 2026
Is nitazene-related mortality underestimated? Findings from an in vivo and ex vivo rat study and pharmacoepidemiological analysis of coroner-reported deaths.
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Chen Shuoqi, Aldabergenov Daniyar, Alotaibi Khalid S, Holland Adam, Moore Robert, Wood Rebecca, Hudson Simon, Milton Holly, Menzies Eleanor, Parks Claire, Lawson Alexander J, Harris Magdalena, Singer Mervyn, Dyson Alex, Copeland Caroline S
Аннотация
INTRODUCTION: Nitazenes are potent synthetic opioids. Following reports questioning their post-mortem stability, nitazene-related deaths may have been underestimated in the United Kingdom. We investigated this using a rat model and regional coronial data, and also present national pharmacoepidemiologic trends in nitazene-related deaths.
METHOD: In vivo/ex vivo study: Anaesthetised Wistar rats (n = 12) received intravenous nitazene (metonitazene, N-desethyl isotonitazene, or N-pyrrolidino etonitazene). Rats were euthanised 15 min post-administration if cardiorespiratory arrest had not already occurred (n = 8). Blood and urine were collected, with repeat blood samples taken following cadaver refrigeration (4 °C) for one week. All samples were immediately frozen (-80 °C). Upon defrosting, half were analysed immediately by liquid chromatography tandem mass spectroscopy with half stored at 4 °C for 1 month before analysis.
PHARMACOEPIDEMIOLOGY: Nitazene deaths were extracted from the National Programme on Substance Use Mortality in March 2025 along with all deaths from the Birmingham & Solihull coronial area (2019-2023). Descriptive analyses were conducted along with exponential smoothing models to compare observed and forecasted deaths in Birmingham & Solihull in 2023.
RESULTS: In vivo/ex vivo study: A small fraction of the nitazene detected in the immediate post-mortem blood sample remained in the post-mortem day 7 blood sample that had been refrigerated for 1 month.
PHARMACOEPIDEMIOLOGY: In Birmingham and Solihull, non-nitazene drug deaths rose 33% in 2023 compared to 2019-2022 (predicted n = 107, actual n = 142). By March 2025, 285 deaths with nitazene detections were reported to the National Programme on Substance Use Mortality, with small clusters in 2021 (n = 23) and 2022 (n = 15) before markedly increasing in 2023 (n = 131). Twelve nitazenes were detected with the predominant nitazene shifting over time (2021: isotonitazene; 2022: N-pyrrolidino etonitazene; 2023: N-desethyl isotonitazene). Coroners deemed nitazenes causative in 90% of cases (n = 256/285).
CONCLUSIONS: Nitazene-related deaths have increased in England, Wales, and Northern Ireland, and may have been underestimated due to post-mortem instability. Urgent public health action is required to reduce nitazene-related harms.
METHOD: In vivo/ex vivo study: Anaesthetised Wistar rats (n = 12) received intravenous nitazene (metonitazene, N-desethyl isotonitazene, or N-pyrrolidino etonitazene). Rats were euthanised 15 min post-administration if cardiorespiratory arrest had not already occurred (n = 8). Blood and urine were collected, with repeat blood samples taken following cadaver refrigeration (4 °C) for one week. All samples were immediately frozen (-80 °C). Upon defrosting, half were analysed immediately by liquid chromatography tandem mass spectroscopy with half stored at 4 °C for 1 month before analysis.
PHARMACOEPIDEMIOLOGY: Nitazene deaths were extracted from the National Programme on Substance Use Mortality in March 2025 along with all deaths from the Birmingham & Solihull coronial area (2019-2023). Descriptive analyses were conducted along with exponential smoothing models to compare observed and forecasted deaths in Birmingham & Solihull in 2023.
RESULTS: In vivo/ex vivo study: A small fraction of the nitazene detected in the immediate post-mortem blood sample remained in the post-mortem day 7 blood sample that had been refrigerated for 1 month.
PHARMACOEPIDEMIOLOGY: In Birmingham and Solihull, non-nitazene drug deaths rose 33% in 2023 compared to 2019-2022 (predicted n = 107, actual n = 142). By March 2025, 285 deaths with nitazene detections were reported to the National Programme on Substance Use Mortality, with small clusters in 2021 (n = 23) and 2022 (n = 15) before markedly increasing in 2023 (n = 131). Twelve nitazenes were detected with the predominant nitazene shifting over time (2021: isotonitazene; 2022: N-pyrrolidino etonitazene; 2023: N-desethyl isotonitazene). Coroners deemed nitazenes causative in 90% of cases (n = 256/285).
CONCLUSIONS: Nitazene-related deaths have increased in England, Wales, and Northern Ireland, and may have been underestimated due to post-mortem instability. Urgent public health action is required to reduce nitazene-related harms.