Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, Zurich, Switzerland.
Department of Forensic Medicine and Imaging, Zurich Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich, Switzerland.
J Anal Toxicol. 2021 Apr 12;45(4):356-367. doi: 10.1093/jat/bkaa092.
Postmortem redistribution (PMR) leads to challenges in postmortem case interpretation. Particularly antidepressants and neuroleptics are expected to undergo PMR based on their physico-chemical 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 O-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.
死后再分布（PMR）导致死后案例解释面临挑战。特别是基于其物理化学性质，预计抗抑郁药和神经安定药会发生 PMR。在当前的研究中，在人类（真实案例）中研究了 20 种抗抑郁药和神经安定药的时间和部位依赖性 PMR；其中五种（西酞普兰、米氮平、喹硫平、利培酮和文拉法辛）进行了详细讨论，同时还讨论了两种代谢物（9-OH-利培酮和 O-去甲文拉法辛）。入院时，利用计算机断层扫描引导的样本采集工作流程（t1）采集股骨髓（pB）和心血（HB）以及组织活检样本（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），手动采集来自同一身体部位的样本。使用液相色谱-串联质谱法进行定量。大多数抗抑郁药和神经安定药显示出明显的时间依赖性浓度变化，表明发生了 PMR。首次提出了喹硫平在 pB 中再分布的两个阶段（早期死后阶段浓度降低，随后浓度增加），与现有文献形成对比的是，利培酮和 9-OH-利培酮在 pB 中的浓度随着时间的推移而增加和降低。文拉法辛及其代谢物仅显示最小的浓度变化，而西酞普兰在 pB 中显示出浓度增加的趋势，米氮平显示出浓度降低的趋势。基于时间依赖性组织数据，可以提出沿着肌肉到 pB、肝到 HB 和肺到 HB 浓度梯度的被动扩散过程，以及细菌降解。总体而言，没有一个案例解释需要调整，这表明在所研究的 24 小时内，抗抑郁药和神经安定药的 PMR 变化似乎与法医案例解释无关。然而，当前研究的局限性（例如，尸体的温度控制储存）可能导致对死后发生的变化估计不足，因此，在进行死后结果的解释时，应始终谨慎行事，考虑到 PMR 现象和个体间的变异性。
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