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.

中文翻译：

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猪经肺部给药后，（合成）大麻素JWH-210，RCS-4和∆9-四氢大麻酚的随时间和温度变化的死后浓度变化。

摘要

在法医毒理学中，由于缺乏有关药物稳定性或PM重新分配（PMR）的数据，对死后（PM）药物浓度的解释可能会很复杂。关于合成大麻素（SC），只有稀疏数据可用，这些数据是从单个病例报告中得出的，而没有任何剂量和消耗时间的知识。因此，进行了一项允许检查SC的PMR的对照猪毒性动力学研究。12只猪的肺剂量分别为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Δ9-四氢大麻酚通过超声雾化器。8小时后，将猪用T61处死，收集相关组织和体液的标本。后来，n  = 6）或4°C（n  = 6），并且分别在24、48和72小时后收集更多样品。酶促裂解和固相萃取后，采用标准添加方法通过液相色谱串联质谱法测定浓度。在肺，肝，肾和胆汁/十二指肠含量以及大脑中观察到高浓度的母体化合物。HO-RCS-4是在PM标本中检测到的最普遍的代谢物。通常，在每个组织和体液中都会发现PM浓度的变化，具体取决于PM间隔和储存温度。