Institute of Legal Medicine, Saarland University, Homburg 66421, Germany.
Institute for Clinical and Experimental Surgery, Saarland University, Homburg 66421, Germany.
J Anal Toxicol. 2023 Mar 24;47(3):236-244. doi: 10.1093/jat/bkac082.
The interpretation of analytical results in forensic postmortem (PM) cases often poses a great challenge, in particular, due to possible PM redistribution (PMR) phenomena. In terms of new synthetic opioids, such data are usually not available and, if so, they are from case reports without the exact knowledge of dose, user habits, time of consumption or PM interval (PMI). Hence, a controlled toxicokinetic pig study was performed allowing the examination of PM tissue distribution and possible PMR of U-47700, tramadol and the main metabolites N-desmethyl-U-47700 and O-desmethyltramadol (ODT). For this purpose, 12 domestic pigs received an intravenous dose of 100 µg/kg body weight (BW) U-47700 or 1,000 µg/kg BW tramadol, respectively. The animals were put to death with T61 8 h after administration, and relevant organs, tissues and body fluids were sampled. Subsequently, the animals were stored at room temperature (RT), and the samples were taken again after 24, 48, and 72 h PM. Following homogenization and solid-phase extraction, quantification was performed applying a standard addition approach and liquid chromatography-tandem mass spectrometry. Only low-to-moderate concentration changes of U-47700, tramadol and their main metabolites were found in the analyzed tissue specimens and body fluids during storage at RT depending on the chosen PMI. On the contrary, a remarkable concentration increase of tramadol was observed in the liver tissue. These findings indicate that both synthetic opioids and their main metabolites are only slightly prone to PMR and central blood might be the matrix of choice for quantification of these substances.
在法医死后（PM）案例中，分析结果的解释常常带来巨大挑战，尤其是由于可能存在 PM 再分布（PMR）现象。对于新型合成阿片类药物，通常没有此类数据，即便有，也只是来自案例报告，而对于剂量、使用者习惯、消耗时间或 PM 间隔（PMI）等信息，则没有确切的了解。因此，进行了一项控制毒性动力学猪研究，以检查 U-47700、曲马多以及主要代谢物 N-去甲基-U-47700 和 O-去甲基曲马多（ODT）的 PM 组织分布和可能的 PMR。为此，12 头国内猪分别接受了 100μg/kg 体重（BW）U-47700 或 1000μg/kg BW 曲马多的静脉注射剂量。给药后 8 小时使用 T61 处死动物，并采集相关器官、组织和体液样本。随后，将动物在室温（RT）下储存，并在 24、48 和 72 小时 PM 后再次采集样本。样品经均质化和固相萃取后，采用标准添加法和液相色谱-串联质谱法进行定量。根据所选 PMI，在 RT 下储存时，仅在分析的组织标本和体液中发现 U-47700、曲马多及其主要代谢物的浓度发生了低至中度变化。相反，在肝组织中观察到曲马多的浓度显著增加。这些发现表明，这两种合成阿片类药物及其主要代谢物都不易发生 PMR，而中心血液可能是这些物质定量检测的首选基质。
