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曲马多死后在兔体内分布和死后扩散的比较研究。

A comparative study of postmortem distribution and postmortem diffusion of tramadol in rabbits.

机构信息

School of Forensic Medicine, Shanxi Medical University, No. 56, Xinjian South Road, Yingze District, Taiyuan, 030001, China.

Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing, 100192, China.

出版信息

Sci Rep. 2023 Jan 30;13(1):1702. doi: 10.1038/s41598-022-25459-w.

DOI:10.1038/s41598-022-25459-w
PMID:36717570
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9886908/
Abstract

In recent years, the cases of tramadol intoxication have become more frequent in many countries. However, most of the previous studies have been based on cases of tramadol intoxication, and the detailed information on the differences between postmortem distribution and diffusion of tramadol remains unclear. To investigate this issue systematically, we established a postmortem distribution model and two postmortem diffusion models. Then, gas chromatography-mass spectrometry (GC/MS) was used to measure the concentrations of tramadol in various biological specimens of fluids and tissues. In postmortem distribution, the results showed an uneven distribution of tramadol in various biological specimens, and the concentrations of tramadol in urine were significantly higher than those in other fluids. In postmortem diffusion, the results showed a dosage-dependent increase of tramadol concentration in most specimens; at all time points from 0.25 to 6 h after postmortem administration, the concentrations of tramadol in fluids were not significantly different from those in tissues, and the concentrations of tramadol in urine were lower than those in both tissues and other fluids in most time points. We recommend a quantitative examination of the specimens of both fluids and tissues to provide more evidence for the forensic identification, and the realization that there is a correlation between the concentrations of fluids and tissues is important for determining antemortem and postmortem administration of tramadol. This information can serve as ancillary data in inferring the contribution of a drug to death in cases of suspected tramadol poisoning.

摘要

近年来,许多国家的曲马多中毒案例变得更加频繁。然而,之前的大多数研究都是基于曲马多中毒的案例,关于曲马多死后分布和扩散差异的详细信息仍不清楚。为了系统地研究这个问题,我们建立了一个死后分布模型和两个死后扩散模型。然后,使用气相色谱-质谱法(GC/MS)测量了各种体液和组织样本中曲马多的浓度。在死后分布中,结果显示曲马多在各种生物样本中的分布不均匀,尿液中的曲马多浓度明显高于其他液体。在死后扩散中,结果显示曲马多浓度随着剂量的增加而增加;在死后给药后 0.25 到 6 小时的所有时间点,体液中的曲马多浓度与组织中的浓度无显著差异,且尿液中的曲马多浓度在大多数时间点均低于组织和其他体液中的浓度。我们建议对体液和组织的标本进行定量检查,为法医鉴定提供更多证据,认识到体液和组织之间的浓度存在相关性对于确定曲马多的生前和死后给药非常重要。这些信息可以作为推断疑似曲马多中毒死亡案件中药物对死亡的影响的辅助数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093d/9886908/a8547daa4973/41598_2022_25459_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093d/9886908/71f07ed31bd5/41598_2022_25459_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093d/9886908/bef98b69ff83/41598_2022_25459_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093d/9886908/a8547daa4973/41598_2022_25459_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093d/9886908/71f07ed31bd5/41598_2022_25459_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093d/9886908/bef98b69ff83/41598_2022_25459_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/093d/9886908/a8547daa4973/41598_2022_25459_Fig3_HTML.jpg

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本文引用的文献

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Short-term mortality following tramadol poisonings in Denmark.丹麦曲马多中毒的短期死亡率。
Basic Clin Pharmacol Toxicol. 2022 Jul;131(1):83-92. doi: 10.1111/bcpt.13741. Epub 2022 May 17.
2
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J Anal Toxicol. 2021 Feb 13;45(2):203-210. doi: 10.1093/jat/bkaa035.
3
Postmortem Brain-Blood Ratios of Codeine, Fentanyl, Oxycodone and Tramadol.体内死后血液与脑组织中可待因、芬太尼、羟考酮和曲马多的浓度比值。
J Anal Toxicol. 2021 Feb 6;45(1):53-59. doi: 10.1093/jat/bkaa048.
4
Distribution of synthetic opioids in postmortem blood, vitreous humor and brain.死后血液、玻璃体和脑组织中合成阿片类药物的分布。
Forensic Sci Int. 2019 Dec;305:109999. doi: 10.1016/j.forsciint.2019.109999. Epub 2019 Oct 21.
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Time-Dependent Postmortem Redistribution of Opioids in Blood and Alternative Matrices.阿片类药物在血液及其他基质中的时间依赖性死后再分布
J Anal Toxicol. 2018 Jul 1;42(6):365-374. doi: 10.1093/jat/bky017.
6
Comparative pharmacology and toxicology of tramadol and tapentadol.曲马多和酒石酸布托啡诺的比较药理学和毒理学。
Eur J Pain. 2018 May;22(5):827-844. doi: 10.1002/ejp.1196. Epub 2018 Feb 19.
7
A 15-year overview of increasing tramadol utilisation and associated mortality and the impact of tramadol classification in the United Kingdom.英国曲马多使用量增加、相关死亡率及曲马多分类影响的15年概述。
Pharmacoepidemiol Drug Saf. 2018 May;27(5):487-494. doi: 10.1002/pds.4320. Epub 2017 Sep 24.
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Evaluation of the Ecstasy influence on tramadol and its main metabolite plasma concentration in rats.摇头丸对大鼠曲马多及其主要代谢物血浆浓度影响的评估。
Drug Metab Pers Ther. 2017 Sep 26;32(3):137-145. doi: 10.1515/dmpt-2017-0018.
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Curr Pharm Des. 2017;23(36):5530-5541. doi: 10.2174/1381612823666170622111739.
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