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检测死后玻璃体液中的完整胰岛素类似物-在法医毒理学案例工作中的应用。

Detection of intact insulin analogues in post-mortem vitreous humour-Application to forensic toxicology casework.

机构信息

Forensic Toxicology Laboratory, ChemCentre, Bentley, Western Australia, Australia.

出版信息

Drug Test Anal. 2021 Mar;13(3):604-613. doi: 10.1002/dta.2974. Epub 2020 Nov 26.

DOI:10.1002/dta.2974
PMID:33197145
Abstract

The application of proteomic techniques to forensic science widens the range of analytical capabilities available to forensic laboratories when answering complex toxicology problems. Currently, these techniques are underutilised in post-mortem toxicology because of the historic focus on smaller (<1,000 amu) drug molecules. Definitive confirmation of an insulin overdose by analysis of post-mortem biological matrices is rare and challenging, however can assist coronial investigations pertaining to accidental or intentional overdoses in both diabetic and nondiabetic populations. A semiautomated micro-solid phase extraction paired with mass spectrometry-based insulin methodology was developed and validated for routine use in a Forensic Coronial Toxicology Laboratory. This resulting work reports the first Australian cases where synthetic insulins were confirmed by mass spectrometry in the vitreous humour of Type 1 diabetics who intentionally or accidentally overdosed on their prescription medication glargine and aspart. The detection of glargine M1 in Case 1, aspart in Case 2 and glargine M1 was indicated in Case 3. This paper highlights advancements in forensic coronial toxicology and the promising potential of proteomic analysis in a forensic context.

摘要

蛋白质组学技术在法医学中的应用拓宽了法医实验室在解决复杂毒理学问题时可用的分析能力范围。目前,由于历史上对较小的(<1000amu)药物分子的关注,这些技术在死后毒理学中未得到充分利用。通过对死后生物基质的分析来明确确认胰岛素过量的情况很少见且具有挑战性,但可以帮助法医调查涉及糖尿病和非糖尿病人群的意外或故意过量用药的情况。本文开发并验证了一种半自动化的微固相萃取与基于质谱的胰岛素方法,以便在法医尸检毒理学实验室中常规使用。这项工作报告了澳大利亚首例通过质谱法在 1 型糖尿病患者的玻璃体中确认合成胰岛素的案例,这些患者故意或意外过量服用了他们的处方药物甘精胰岛素和门冬胰岛素。在案例 1 中检测到甘精胰岛素 M1,在案例 2 中检测到门冬胰岛素,在案例 3 中检测到甘精胰岛素 M1。本文强调了法医尸检毒理学的进展以及蛋白质组学分析在法医环境中的有前途的潜力。

相似文献

1
Detection of intact insulin analogues in post-mortem vitreous humour-Application to forensic toxicology casework.检测死后玻璃体液中的完整胰岛素类似物-在法医毒理学案例工作中的应用。
Drug Test Anal. 2021 Mar;13(3):604-613. doi: 10.1002/dta.2974. Epub 2020 Nov 26.
2
Post-mortem vitreous humour as potential specimen for detection of insulin analogues by LC-MS/MS.死后玻璃体作为通过 LC-MS/MS 检测胰岛素类似物的潜在标本。
Forensic Sci Int. 2013 Dec 10;233(1-3):328-32. doi: 10.1016/j.forsciint.2013.10.009. Epub 2013 Oct 14.
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Validation of a Fully Automated Immunoaffinity Workflow for the Detection and Quantification of Insulin Analogs by LC-MS-MS in Postmortem Vitreous Humor.验证 LC-MS-MS 法检测死后玻璃体液中胰岛素类似物的完全自动化免疫亲和工作流程的有效性。
J Anal Toxicol. 2019 Aug 23;43(7):505-511. doi: 10.1093/jat/bkz014.
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Measuring insulin in human vitreous humour using LC-MS/MS.使用 LC-MS/MS 测定人玻璃体中的胰岛素。
Drug Test Anal. 2012 Jan;4(1):53-6. doi: 10.1002/dta.368. Epub 2011 Nov 18.
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Vitreous humour - routine or alternative material for analysis in forensic medicine.玻璃体液——法医学分析的常规或替代材料。
Arch Med Sadowej Kryminol. 2017;67(3):201-213. doi: 10.5114/amsik.2017.73192.
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Determination of hypoglycaemia induced by insulin or its synthetic analogues post mortem.死后胰岛素或其合成类似物引起低血糖的测定。
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Development and validation of an ESI-LC-MS/MS method for simultaneous identification and quantification of 24 analytes of forensic relevance in vitreous humour, whole blood and plasma.用于同时鉴定和定量玻璃体液、全血和血浆中24种法医相关分析物的电喷雾电离液相色谱-串联质谱法的开发与验证
Drug Test Anal. 2016 Jan;8(1):86-97. doi: 10.1002/dta.1797. Epub 2015 Apr 27.
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Comments on 'Measuring insulin in human vitreous humour using LC-MS/MS' by Thevis et al.
Drug Test Anal. 2013 Feb;5(2):133-4. doi: 10.1002/dta.1392. Epub 2012 Aug 9.
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Prolonged glucose requirements after intentional glargine and aspart overdose.甘精胰岛素和门冬胰岛素故意过量使用后对葡萄糖的需求延长。
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Vitreous humour as an alternative material for the determination of alcohol concentration in human corpses.玻璃体液作为测定人体尸体酒精浓度的替代材料。
Arch Med Sadowej Kryminol. 2018;68(2):108-118. doi: 10.5114/amsik.2018.77923.

引用本文的文献

1
First Dimension Trap-and-Elute Combined with Second Dimension Reversed-Phase Liquid Chromatography Separation Using a Two-Dimensional-Liquid Chromatography-Tandem Mass Spectrometry System for Sensitive Quantification of Human Insulin and Six Insulin Analogs in Plasma: Improved Chromatographic Resolution and Stability Testing.使用二维液相色谱 - 串联质谱系统,采用一维捕集洗脱与二维反相液相色谱分离相结合的方法对血浆中人类胰岛素和六种胰岛素类似物进行灵敏定量:改进的色谱分辨率和稳定性测试
J Sep Sci. 2025 Feb;48(2):e70092. doi: 10.1002/jssc.70092.
2
Insulin overdose with fatal outcome?: Two forensic cases.胰岛素过量导致致命后果?两例法医案例。
Toxicol Rep. 2024 May 11;12:542-545. doi: 10.1016/j.toxrep.2024.05.004. eCollection 2024 Jun.
3
The Role of Protein Degradation in Estimation Postmortem Interval and Confirmation of Cause of Death in Forensic Pathology: A Literature Review.蛋白质降解在法医病理学中推断死亡时间和死因确认中的作用:文献综述。
Int J Mol Sci. 2024 Jan 29;25(3):1659. doi: 10.3390/ijms25031659.