合成大麻素 cumyl-5F-P7AICA 及其 N-戊酸代谢物在死后的浓度变化是否取决于环境条件?- 猪肺部给药后的系统研究

IF 2.9 3区 医学 Q2 TOXICOLOGY Toxicology letters Pub Date : 2024-10-10 DOI:10.1016/j.toxlet.2024.10.006
Nadja Walle , Adrian A. Doerr , Benjamin Peters , Matthias W. Laschke , Michael D. Menger , Peter H. Schmidt , Markus R. Meyer , Nadine Schaefer
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引用次数: 0

摘要

涉及合成大麻素(SC)的死亡病例数量正在增加。然而,由于合成大麻素的时间间隔未知,以及可能的再分布过程或不稳定性,对死后毒理学发现的解释具有挑战性。有关 SCs 的数据十分稀少。因此,我们进行了一项猪对照研究,以确定在不同环境条件下积雪-5F-P7AICA 的 PM 稳定性。十头猪每人吸入 200 微克/千克体重的 cumyl-5F-P7AICA。六小时后,将它们安乐死,并对主要组织和体液进行活检。将动物保存在空气或水中(各 5 只),并在三天内反复采集样本。积雪草-5F-P7AICA 及其 N-戊酸代谢物(NPA)的定量采用标准添加法或经过充分验证的方法(血液),然后进行 LC-MS/MS。在这两种条件下,肝脏、胆汁液和肌肉标本中的积雪-5F-P7AICA 浓度变化都与时间有关。只有在空气中储存的动物十二指肠中,NPA 的浓度才会发生显著变化。只有肾脏中的积雪-5F-P7AICA 和十二指肠中的 NPA 代谢物的浓度变化与环境有关。总的来说,积雪草-5F-P7AICA 及其代谢物在 PM 标本中似乎相当稳定。因此,如果没有外周血,也可以对中心血进行分析。
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Are the postmortem concentration changes of the synthetic cannabinoid cumyl-5F-P7AICA and its N-pentanoic acid metabolite dependent on the environmental conditions? – A systematic study following pulmonary administration to pigs
The number of fatal cases involving synthetic cannabinoids (SCs) is increasing. However, interpretation of postmortem (PM) toxicological findings is challenging, due to unknown PM intervals and possible redistribution processes or instabilities. Only sparse data on SCs are available. Therefore, a controlled pig study was performed to determine the PM stability of cumyl-5F-P7AICA under different environmental conditions. Ten pigs inhalatively received 200 µg/kg body weight cumyl-5F-P7AICA each. Six hours later, they were euthanized and biopsies of the main tissues and body fluids were taken. Animals were stored in air or water (n=5 each) and samples were repeatedly taken for three days. Quantification of cumyl-5F-P7AICA and its N-pentanoic acid metabolite (NPA) was performed using standard addition or a fully validated method (blood) followed by LC-MS/MS. Time-dependent concentration changes of cumyl-5F-P7AICA were observed in liver, bile fluid and muscle specimens at both conditions. Concentrations of NPA only changed considerably in duodenum content of animals stored in air. Environment-dependent concentrations changes were only observed for cumyl-5F-P7AICA in kidney and the NPA metabolite in duodenum content. Overall, cumyl-5F-P7AICA and its metabolite seem to be quite stable in PM specimens. Hence, also central blood might be analyzed, if no peripheral blood is available.
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来源期刊
Toxicology letters
Toxicology letters 医学-毒理学
CiteScore
7.10
自引率
2.90%
发文量
897
审稿时长
33 days
期刊介绍: An international journal for the rapid publication of novel reports on a range of aspects of toxicology, especially mechanisms of toxicity.
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