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通过废水分析早期识别强效苄基苯并咪唑类药物(硝氮烯)的使用情况:来自22个国家的两年数据。

Early identification of the use of potent benzylbenzimidazoles (nitazenes) through wastewater analysis: Two years of data from 22 countries.

作者信息

Bade Richard, Nadarajan Dhayaalini, Hall Wayne, Brown Jared A, Schumann Jennifer

机构信息

Queensland Alliance for Environmental Health Sciences (QAEHS), The University of Queensland, Dutton Park, Australia.

National Centre for Youth Substance Use Research, The University of Queensland, St Lucia, Australia.

出版信息

Addiction. 2025 Mar 18. doi: 10.1111/add.70027.

DOI:10.1111/add.70027
PMID:40099983
Abstract

BACKGROUND AND AIMS

The use of new synthetic opioids, such as the highly potent 2-benzylbenzimidazoles (i.e. nitazene) drugs, is a global health concern because of their increased risk of fatal overdose. In the early 2020s, nitazene analogues were linked to significant numbers of overdoses in the United States. Their reach is now worldwide, with nitazene overdose deaths reported in Europe, Australia and New Zealand. The aim of this study was to measure quantities of nitazenes in wastewater samples collected from 68 locations in 22 countries, covering six continents, to understand and estimate their use.

METHODS

Untreated influent wastewater samples were collected over a one-week period that included the New Year period in 2022-2023 and 2023-2024. Samples were collected from 22 countries: Australia, Austria, Belgium, Brazil, Canada, Chile, China, Cyprus, Czechia, France, Germany, Greece, Iceland, Italy, New Zealand, Nigeria, Republic of Korea, Slovenia, Spain, Sweden, United Kingdom and United States. Samples were loaded onto solid-phase extraction cartridges in the country of collection and sent to Australia for elution and analysis using sensitive liquid chromatography-mass spectrometry methods.

RESULTS

A total of 683 individual wastewater samples were analysed across the two years: 339 in 2022-2023 and 344 in 2023-2024. Two nitazene analogues-protonitazene and N-pyrrolidino etonitazene (etonitazepyne)-were found in five separate sites in the United States and Australia. In the 2022-2023 period, protonitazene was found in two sites in the United States. The following year, protonitazene was detected in two further sites in the United States, while both protonitazene and etonitazepyne were found in one site in Australia. Protonitazene mass loads ranged between 0.3 mg/day/1000 people and 100 mg/day/1000 people. Etonitazepyne was also found at mass loads between 0.2-2 mg/day/1000 people).

CONCLUSIONS

A very high mass load of protonitazene was calculated, using wastewater analysis, for the day of 30 December 2023 in one site in Australia. Etonitazepyne showed the same trend from a lower base. Wastewater-based nitazene surveillance shows promise as a form of both drug early warning and ongoing monitoring of trends in use, especially as a complementary tool to existing surveillance methods.

摘要

背景与目的

新型合成阿片类药物的使用,如高效的2-苄基苯并咪唑类(即硝氮烯)药物,因其致命过量风险增加而成为全球健康问题。在21世纪20年代初,硝氮烯类似物与美国大量过量用药事件有关。如今其影响已遍及全球,欧洲、澳大利亚和新西兰都报告了硝氮烯过量死亡事件。本研究的目的是测量从六大洲22个国家的68个地点采集的废水样本中的硝氮烯含量,以了解并估计其使用情况。

方法

在2022 - 2023年和2023 - 2024年包括新年期间的一周内收集未经处理的进水废水样本。样本来自22个国家:澳大利亚、奥地利、比利时、巴西、加拿大、智利、中国、塞浦路斯、捷克、法国、德国、希腊、冰岛、意大利、新西兰、尼日利亚、韩国、斯洛文尼亚、西班牙、瑞典、英国和美国。样本在采集国加载到固相萃取柱上,然后送往澳大利亚,使用灵敏的液相色谱 - 质谱法进行洗脱和分析。

结果

两年共分析了683个单独的废水样本:2022 - 2023年为339个,2023 - 2024年为344个。在美国和澳大利亚的五个不同地点发现了两种硝氮烯类似物——质子化硝氮烯和N - 吡咯烷基乙硝氮烯(乙硝氮烯炔)。在2022 - 2023年期间,在美国的两个地点发现了质子化硝氮烯。次年,在美国又有两个地点检测到质子化硝氮烯,同时在澳大利亚的一个地点发现了质子化硝氮烯和乙硝氮烯炔。质子化硝氮烯的质量负荷范围在0.3毫克/天/1000人至100毫克/天/1000人之间。乙硝氮烯炔的质量负荷也在0.2 - 毫克/天/1000人之间。

结论

通过废水分析计算得出,2023年12月30日澳大利亚一个地点的质子化硝氮烯质量负荷非常高。乙硝氮烯炔从较低基数呈现相同趋势。基于废水的硝氮烯监测有望成为药物早期预警和持续监测使用趋势的一种形式,特别是作为现有监测方法补充工具。

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本文引用的文献

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Identification of nitazene-related deaths in Australia: How do we make it accurate and timely?澳大利亚硝氮烯相关死亡案例的识别:我们如何做到准确且及时?
Drug Alcohol Rev. 2025 Feb 17. doi: 10.1111/dar.14028.
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In vitro structure-activity relationships and forensic case series of emerging 2-benzylbenzimidazole 'nitazene' opioids.新型苯并咪唑类“硝甲西泮”类阿片的体外构效关系和法医案例系列
Arch Toxicol. 2024 Sep;98(9):2999-3018. doi: 10.1007/s00204-024-03774-7. Epub 2024 Jun 14.
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In vitro characterization of protonitazene metabolites, using human liver microsomes, and first application to two urines collected from death cases.
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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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Identification of N-pyrrolidino protonitazene in powders sold as heroin and associated with overdose clusters in Dublin and Cork, Ireland.在爱尔兰都柏林和科克被当作海洛因售卖且与过量用药群体相关的粉末中鉴定出N-吡咯烷基质子氮杂环庚三烯。
Drug Test Anal. 2025 Mar;17(3):350-357. doi: 10.1002/dta.3707. Epub 2024 May 20.
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