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时间和温度依赖性死后浓度变化的(合成)大麻素 JWH-210 , RCS-4 ,以及 ∆ 9 -四氢大麻酚肺给药后猪。

Time- and temperature-dependent postmortem concentration changes of the (synthetic) cannabinoids JWH-210, RCS-4, as well as ∆9-tetrahydrocannabinol following pulmonary administration to pigs.

机构信息

Institute of Legal Medicine, Saarland University, Building 49.1, 66421, Homburg, Germany.

Institute for Clinical and Experimental Surgery, Saarland University, Building 65/66, 66421, Homburg, Germany.

出版信息

Arch Toxicol. 2020 May;94(5):1585-1599. doi: 10.1007/s00204-020-02707-4. Epub 2020 Mar 18.

Abstract

In forensic toxicology, interpretation of postmortem (PM) drug concentrations might be complicated due to the lack of data concerning drug stability or PM redistribution (PMR). Regarding synthetic cannabinoids (SC), only sparse data are available, which derived from single case reports without any knowledge of dose and time of consumption. Thus, a controlled pig toxicokinetic study allowing for examination of PMR of SC was performed. Twelve pigs received a pulmonary dose of 200 µg/kg BW each of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone (RCS-4), and Δ9-tetrahydrocannabinol via an ultrasonic nebulizer. Eight hours after, the pigs were put to death with T61 and specimens of relevant tissues and body fluids were collected. Subsequently, the animals were stored at room temperature (n = 6) or 4 °C (n = 6) and further samples were collected after 24, 48, and 72 h each. Concentrations were determined following enzymatic cleavage and solid-phase extraction by liquid-chromatography tandem mass spectrometry applying the standard addition approach. High concentrations of the parent compounds were observed in lung, liver, kidney and bile fluid/duodenum content as well as brain. HO-RCS-4 was the most prevalent metabolite detected in PM specimens. In general, changes of PM concentrations were found in every tissue and body fluid depending on the PM interval as well as storage temperature.

摘要

在法医毒理学中,由于缺乏有关药物稳定性或死后再分布(PMR)的数据,死后药物浓度的解释可能会变得复杂。关于合成大麻素(SC),只有很少的数据来自于没有剂量和消费时间知识的单一病例报告。因此,进行了一项控制猪毒代动力学研究,以检查 SC 的 PMR。12 头猪通过超声雾化器每头接受 200µg/kg BW 的 4-乙基萘-1-基-(1-戊基-吲哚-3-基)甲酮(JWH-210)、2-(4-甲氧基苯基)-1-(1-戊基-吲哚-3-基)甲酮(RCS-4)和 Δ9-四氢大麻酚的肺内剂量。8 小时后,用 T61 将猪处死,并收集相关组织和体液的标本。随后,将动物在室温(n=6)或 4°C(n=6)下储存,并在 24、48 和 72 小时后分别收集进一步的样本。采用液质联用串联质谱法,通过酶切和固相萃取,应用标准添加法测定浓度。在肺、肝、肾和胆汁液/十二指肠内容物以及脑中观察到母体化合物的高浓度。HO-RCS-4 是 PM 标本中检测到的最普遍的代谢物。一般来说,根据 PM 间隔和储存温度,每种组织和体液中的 PM 浓度都会发生变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aa0/7261730/449556424edf/204_2020_2707_Fig1_HTML.jpg

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