Time- and Site-Dependent Postmortem Redistribution of Antidepressants and Neuroleptics in Blood and Alternative Matrices
Time- and Site-Dependent Postmortem Redistribution of Antidepressants and Neuroleptics in Blood and Alternative Matrices
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DOI：
10.1093/jat/bkaa092
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发表时间：
2021-05-01
影响因子：
2.5
通讯作者：
Steuer, Andrea E.
中科院分区：
文献类型：
--
作者：
Brockbals, Lana;Staeheli, Sandra N.;Steuer, Andrea E.
死后重新分配（PMR）给死后案件解释带来了挑战。特别是抗抑郁药和精神安定药预计将根据其理化特性进行 PMR。在当前的研究中，我们对 20 种抗抑郁药和精神安定药的时间和部位依赖性 PMR 进行了人体研究（真实病例）；详细讨论了其中五种（西酞普兰、米氮平、喹硫平、利培酮和文拉法辛）以及两种代谢物（9-OH-利培酮和0-去甲基文拉法辛）。进入该研究所后，利用计算机断层扫描引导的样本收集工作流程（t1）收集血液[股动脉（pB）和心脏血（HB）]和组织活检样本（肺、肾、肝、脾、大腿肌肉和脂肪组织）。大约 24 小时后（t2；平均 23 +/- 9.3 小时），手动收集来自同一身体区域的样本。使用液相色谱-串联质谱法进行定量。大多数抗抑郁药和精神安定药表现出显着的时间依赖性浓度变化，表明 PMR 的发生。首次提出了喹硫平在 pB 中重新分布的两个阶段（死后早期浓度降低，随后浓度增加），并且与现有文献相比，观察到利培酮和 9-OH-利培酮的 pB 浓度随着时间的推移而增加和减少。随着时间的推移，文拉法辛及其代谢物仅表现出最小的浓度变化，而西酞普兰表现出浓度增加的趋势，而米氮平则表现出浓度随pB下降的趋势。基于时间依赖性组织数据，沿着肌肉到 pB、肝脏到 HB 和肺到 HB 浓度梯度的被动扩散过程可以与细菌降解一起提出。总体而言，无需调整案例解释，这表明抗抑郁药和精神安定药的 PMR 变化似乎与所调查的 24 小时内的法医案例解释无关。然而，当前研究的局限性（例如，尸体的温度控制储存）可能导致低估发生的尸检变化，因此，对尸检结果的解释应始终谨慎进行，考虑到PMR现象和个体间的变异性。
Postmortem redistribution (PMR) leads to challenges in postmortem case interpretation. Particularly antidepressants and neuroleptics are expected to undergo PMR based on their physicochemical properties. For the current study, time- and site-dependent PMR of 20 antidepressants and neuroleptics were investigated in humans (authentic cases); five of which are discussed in detail (citalopram, mirtazapine, quetiapine, risperidone and venlafaxine) along with two metabolites (9-OH-risperidone and 0-desmethylvenlafaxine). Blood [femoral (pB) and heart blood (HB)] and tissue biopsy samples (lung, kidney, liver, spleen, thigh muscle and adipose tissue) were collected upon admission to the institute utilizing a computed tomography-guided sample collection workflow (t1). Approximately 24 h later (t2; mean 23 +/- 9.3 h), samples from the same body regions were collected manually. Liquid chromatography-tandem mass spectrometry was used for quantification. Most antidepressants and neuroleptics showed significant time-dependent concentration changes indicating the occurrence of PMR. For the first time, two phases of redistribution in pB for quetiapine were proposed (concentration decreases in the early postmortem phase, followed by concentration increases) and contrasting existing literature, both concentration increases and decreases in pB overtime were observed for risperidone and 9-OH-risperidone. Venlafaxine and its metabolite only showed minimal concentration changes, while citalopram exhibited a trend for concentration increases and mirtazapine for concentration decreases in pB overtime. Based on time-dependent tissue data, passive diffusion processes along the muscle-to-pB, liver-to-HB and lung-to-HB concentration gradients could be proposed along with bacterial degradation. Overall, no case interpretation had to be adjusted, which suggests that PMR changes of antidepressants and neuroleptics do not seem to be relevant for forensic case interpretation within the 24 h period that was investigated. However, limitations of the current study (e.g., temperature-controlled storage of the bodies) could have led to an underestimation of occurring postmortem changes, hence, interpretation of postmortem results should always be conducted with care, considering PMR phenomena and inter-individual variability.