Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs?

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-07-02 DOI:10.1007/s00204-024-03815-1
Adrian A. Doerr, Frederike Nordmeier, Nadja Walle, Matthias W. Laschke, Michael D. Menger, Markus R. Meyer, Peter H. Schmidt, Nadine Schaefer
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Abstract

Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC–MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.

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猪肺部给药后,组织和体液中 7 种氮杂环吲哚衍生合成大麻素 5F-MDMB-P7AICA 的浓度是否会受到死后重新分布的影响?
据报道,许多致命的中毒事件都与服用较新的强效合成大麻素有关。然而,可能出现的死后再分布(PMR)可能会使分析结果的可靠解释变得复杂。因此,有必要研究新型合成大麻素的 PMR 潜力。猪模型已被证明适用于这一目的。因此,本研究旨在研究合成大麻素 5F-MDMB-P7AICA 及其主要代谢物 5F-MDMB-P7AICA-二甲基丁酸(DBA)的 PMR。麻醉和通气猪吸入 5F-MDMB-P7AICA(每公斤体重 200 微克)。实验结束后,对动物实施安乐术,并在室温下保存 3 天。每天采集组织和体液样本。样本经固相萃取后使用标准添加法和 LC-MS/MS 进行分析,血液经蛋白质沉淀后使用有效方法进行定量。在死前样本中,5F-MDMB-P7AICA 主要存在于脂肪组织、胆汁液和十二指肠内容物中。在血液、肌肉、大脑、肝脏和肺中发现了少量的 5F-MDMB-P7AICA。高浓度的 DBA 主要存在于胆汁、十二指肠内容物、尿液和肾脏/肾周脂肪组织中。在其余组织中,发现的含量相当低。与较早的合成大麻素相比,5F-MDMB-P7AICA 的 PMR 不太明显。血液中的浓度在死后似乎也相对稳定在较低水平。如果没有血液样本,肌肉、肾脏、脂肪和十二指肠内容物是检测 5F-MDMB-P7AICA 和 DBA 的合适替代基质。总之,5F-MDMB-P7AICA 及其主要代谢物 DBA 的浓度不会受到 PMR 的影响。
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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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