合成大麻素 ADB-BUTINACA 和 ADB-4en-PINACA 的代谢及其在法医毒理学案例和监狱中查获的注入文件中的检测,Drug Testing and Analysis

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合成大麻素 ADB-BUTINACA 和 ADB-4en-PINACA 的代谢及其在法医毒理学案例和监狱中查获的注入文件中的检测
Drug Testing and Analysis ( IF 2.6 ) Pub Date : 2021-11-22 , DOI: 10.1002/dta.3203
Robert Kronstrand _{1,

2} , Caitlyn Norman ₃ , Svante Vikingsson _{1,

2,

4} , Anoek Biemans ₂ , Bryan Valencia Crespo ₅ , Darren Edwards ₆ , Daniel Fletcher _{6,

7} , Nicolas Gilbert ₈ , Mattias Persson ₁ , Robert Reid ₃ , Olga Semenova ₆ , Faisal Al Teneiji _{3,

9} , Xiongyu Wu ₅ , Johan Dahlén ₅ , Niamh NicDaéid ₃ , Fuad Tarbah ₉ , Oliver B Sutcliffe ₈ , Craig McKenzie _{3,

10} , Henrik Gréen _{1,

2}

Affiliation

Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Leverhulme Research Centre for Forensic Science, School of Science and Engineering, University of Dundee, Dundee, UK.
RTI International, Research Triangle, North Carolina, USA.
Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK.
BioAscent, Motherwell, UK.
Department of Natural Sciences, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
General Department of Forensic Science and Criminology, Toxicology Department, Dubai Police, Dubai, United Arab Emirates.
Chiron AS, Trondheim, Norway.

早期预警系统检测新的精神活性物质 (NPS)，而专门的监测计划以及常规药物和毒理学测试可识别流行率的波动。我们报告了合成大麻素受体激动剂 (SCRA) ADB-BUTINACA ( N -[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1 H ) 的日益流行-吲唑-3-羧酰胺）。ADB-BUTINACA 于 2019 年在瑞典的一次缉获中首次被发现，不久之后我们在 13 例瑞典法医毒理学常规病例中报告了其发现。2021 年 1 月，在苏格兰监狱查获的注入 SCRA 的纸张中检测到 ADB-BUTINACA，并且其流行率迅速上升，在 2021 年 1 月至 2021 年 7 月期间测试的注入 SCRA 的纸张中检测到 60.4%。在这项工作中，ADB-BUTINACA与人肝细胞 (HHeps) 一起孵育，在体外鉴定出 21 种代谢物，在真实病例样本中检测到 14 种。母体药物和代谢物 B9（ n上的单羟基化-丁基尾）和 B16（吲唑环上的单羟基化）是推荐的血液生物标志物，而代谢物 B4（在吲唑核心上形成二氢二醇）、B9 和 B16 是尿液中合适的生物标志物。ADB-4en-PINACA ( N -[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1 H -indazole-3-carboxamide ) 于 2020 年 12 月在苏格兰监狱中被发现，但与 ADB-BUTINACA 不同，流行率一直很低。ADB-4en-PINACA 与 HHeps 一起孵育，鉴定出 11 种代谢物。代谢物 E3（在尾部形成的二氢二醇）和 E7（连接/头部基团上的羟基化）是体外最丰富的代谢物，被建议作为尿生物标志物。ADB-BUTINACA (EC ₅₀ , 11.5 nM 和 ADB-4en-PINACA (EC₅₀ , 11.6 nM) 类似于 MDMB-4en-PINACA (EC ₅₀ , 4.3 nM)。在监狱样本中还检测到了第三种叔-亮氨酰胺 SCRA，ADB-HEXINACA，需要进一步调查。

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The metabolism of the synthetic cannabinoids ADB-BUTINACA and ADB-4en-PINACA and their detection in forensic toxicology casework and infused papers seized in prisons

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC₅₀, 11.5 nM and ADB-4en-PINACA (EC₅₀, 11.6 nM) are similar to that of MDMB-4en-PINACA (EC₅₀, 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation.

更新日期：2021-11-22

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