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涉及环丙基芬太尼的致命中毒——死后时间依赖性再分布的调查

Fatal poisoning involving cyclopropylfentanyl - Investigation of time-dependent postmortem redistribution.

作者信息

Brockbals Lana, Staeheli Sandra N, Gentile Simon, Schlaepfer Markus, Bissig Christian, Bolliger Stephan A, Kraemer Thomas, Steuer Andrea E

机构信息

Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.

Department of Forensic Medicine & Imaging, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.

出版信息

Forensic Sci Int. 2019 Jan;294:80-85. doi: 10.1016/j.forsciint.2018.11.007. Epub 2018 Nov 16.

DOI:10.1016/j.forsciint.2018.11.007
PMID:30497048
Abstract

A growing number of fatal overdoses involving opioid drugs, in particular involving fentanyl and its analogues, pose an immense threat to public health. Postmortem casework of forensic toxicologists in such cases is challenging, as data on pharmacodynamic and pharmacokinetic properties as well as reference values for acute toxicities and data on potential postmortem redistribution (PMR) mechanisms often do not exist. A fatal case involving cyclopropylfentanyl was investigated at the Zurich Institute of Forensic Medicine and the Zurich Forensic Science Institute; an unknown powder found at the scene was reliably identified as cyclopropylfentanyl by gas chromatography-infrared spectroscopy (GC-IR). Femoral blood samples were collected at two time points after death; 11h postmortem (t1) and during the medico-legal autopsy 29h after death (t2). At the autopsy, additional samples from the heart blood, urine and gastric content were collected. Cyclopropylfentanyl was quantified using a validated liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Femoral blood concentration of cyclopropylfentanyl at autopsy was 19.8ng/mL (t1=15.7ng/mL; heart blood concentration at autopsy=52.4ng/mL). In the light of the current literature and under the exclusion that no other morphological findings could explain the cause of death, contribution of cyclopropylfentanyl to death was proposed (polydrug use). Significant postmortem concentration increases of cyclopropylfentanyl in femoral blood during 18h after the first sampling were observed, thus indicating a relevant potential to undergo PMR. A central-to-peripheral blood concentration ratio of 2.6 supports this. Consequently, the current case suggests that postmortem cyclopropylfentanyl concentration should always be interpreted with care.

摘要

越来越多涉及阿片类药物,尤其是芬太尼及其类似物的致命过量用药事件,对公众健康构成了巨大威胁。在此类案件中,法医毒理学家的尸检工作颇具挑战性,因为关于药效学和药代动力学特性的数据,以及急性毒性参考值和潜在的死后再分布(PMR)机制的数据往往并不存在。苏黎世法医学研究所和苏黎世法医学科学研究所对一起涉及环丙基芬太尼的致命案件进行了调查;现场发现的一种未知粉末通过气相色谱 - 红外光谱法(GC - IR)被可靠地鉴定为环丙基芬太尼。在死亡后的两个时间点采集了股血样本;死后11小时(t1)和死后29小时进行法医尸检时(t2)。尸检时,还采集了来自心脏血液、尿液和胃内容物的额外样本。使用经过验证的液相色谱 - 串联质谱法(LC - MS/MS)对环丙基芬太尼进行定量。尸检时股血中环丙基芬太尼的浓度为19.8ng/mL(t1 = 15.7ng/mL;尸检时心脏血液浓度 = 52.4ng/mL)。根据当前文献,并在排除没有其他形态学发现可以解释死亡原因的情况下,提出环丙基芬太尼对死亡有贡献(多药使用)。在首次采样后的18小时内,观察到股血中环丙基芬太尼的死后浓度显著增加,因此表明其具有进行死后再分布的相关潜力。中心血与外周血浓度比为2.6支持了这一点。因此,当前案例表明,对死后环丙基芬太尼浓度的解读应始终谨慎。

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