Available literature demonstrates that methadone is prone to moderate postmortem redistribution, but subject to high interindividual variability in the central to peripheral blood concentration ratios (C/P). In this case series, 10 cases of chronic methadone users displaying C/P < 1 (range 0.26–0.82) are described. Femoral, cardiac and ante-mortem blood concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) are reported for all cases, as well as sex, age, case history, results of the pathological investigation, other toxicological findings and cause and manner of death. EDDP blood concentrations, similar in both central and peripheral blood, as well as ante-mortem blood concentration results in Case 4, demonstrate that this atypical C/P < 1 finding is attributable to postmortem changes and not analytical or pre-analytical artifacts. Case 4 is a particularly instructive example, with femoral blood concentration (966 ng/mL) approximately twice as high as cardiac blood (499 ng/mL) and ante-mortem blood (418 ng/mL, collected 38 min prior to death)—clearly demonstrating that cardiac blood methadone concentration is more representative of the ante-mortem blood concentration in this case. In Case 4 and four others, toxicological interpretation based on femoral blood concentration alone would have been misleading. Based on these results and evidence from the literature, it is hypothesized that methadone bioaccumulates in the tissues of chronic users and redistributes from thigh tissues into femoral blood, increasing the concentration postmortem. This case series highlights how femoral blood is not always preserved from postmortem changes and that the analysis of multiple blood sources is necessary to avoid a misleading toxicological interpretation—particularly for cases of chronic methadone users.

中文翻译：

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长期美沙酮使用者的非典型死后再分布

现有文献表明，美沙酮死后易于发生中度再分布，但中心血与外周血浓度比 (C/P) 存在较高的个体差异。在该病例系列中，10 例慢性美沙酮使用者的 C/P ＜0。1（范围 0.26–0.82）进行了描述。报告所有病例的股骨、心脏和生前血液中美沙酮及其代谢物 2-亚乙基-1,5-二甲基-3,3-二苯基吡咯烷 (EDDP) 的浓度，以及性别、年龄、病史、结果病理学调查、其他毒理学结果以及死亡原因和方式。中心血和外周血中的 EDDP 血液浓度以及病例 4 中的死前血液浓度结果相似，表明这种非典型 C/P < 1。1 发现归因于事后变化，而不是分析或分析前的人为因素。病例 4 是一个特别有启发性的例子，股血浓度 (966 ng/mL) 大约是心脏血 (499 ng/mL) 和生前血 (418 ng/mL，死前 38 分钟采集) 的两倍——清楚地表明，在这种情况下，心脏血液美沙酮浓度更能代表生前血液浓度。在案例 4 和其他四个案例中，仅基于股血浓度的毒理学解释可能会产生误导。根据这些结果和文献证据，假设美沙酮在长期使用者的组织中生物蓄积，并从大腿组织重新分布到股骨血液中，从而增加死后的浓度。该病例系列强调了股血并不总是能够免受死后变化的影响，并且有必要对多种血液来源进行分析，以避免误导性的毒理学解释——特别是对于长期美沙酮使用者的病例。