Post-metabolism impurity profiling of carfentanil, remifentanil, sufentanil, and benzylfentanyl

IF 2.6 3区医学 Q2 CHEMISTRY, ANALYTICAL

Forensic Chemistry Pub Date : 2024-05-29 DOI:10.1016/j.forc.2024.100587

Daan Vangerven , Mirjam de Bruin-Hoegée , Fleur Kerstens , Meike Kerklaan , Rowdy P.T. Bross , Alex Fidder , Marcel J. van der Schans , Daan Noort , Arian C. van Asten

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Abstract

Carfentanil, remifentanil, and sufentanil are potent fentanyl analogues that are regularly mixed with illicit drugs causing many overdose deaths. Chemical impurity profiling of these drugs is a well-established technique for linking evidence found at a crime scene to other seized samples. The current study aims to expand the application of impurity profiling to metabolized samples to find synthesis specific markers. This is particularly relevant when the drug has been consumed, and no intact material is present at a crime scene. Carfentanil, remifentanil, and sufentanil were synthesized according to the Ugi or 7-step method and benzylfentanyl was produced using the Siegfried method. After in-vitro metabolism with human liver microsomes, the samples were analyzed by gas chromatography-mass spectrometry (GC–MS) and liquid chromatography high resolution tandem mass spectrometry (LC-HRMS/MS). Characteristic markers were found by applying a match criterion approach and principal component analysis (PCA). The precursors 4-ANBP, aniline, and N-phenylacetamide and several metabolites were identified in post-metabolism samples, indicating that specific synthesis information is retained after in-vitro metabolism. The detected levels were in line with concentrations reported in case work. In addition, LDA was applied to maximize discrimination between synthesis methods and to establish likelihood ratios (LRs). Calibrated LR values were in the range of 0.083 to 16 with very low false positive and false negative error rates. In conclusion, the presented work demonstrates the possibility of combining chemical profiling and retrospective biomarker analysis to obtain information about the synthesis method, which could be useful for forensic reconstructions and attribution investigations.

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卡芬太尼、瑞芬太尼、舒芬太尼和苄芬太尼代谢后杂质谱分析

卡芬太尼（carfentanil）、瑞芬太尼（remifentanil）和舒芬太尼（sufentanil）是强效芬太尼类似物，经常与非法药物混合使用，导致许多吸毒过量死亡。对这些药物进行化学杂质分析是一种行之有效的技术，可将犯罪现场发现的证据与其他缴获的样本联系起来。目前的研究旨在将杂质分析的应用范围扩大到代谢样本，以找到特定的合成标记物。当毒品已被吸食，而犯罪现场又没有完整的物质时，这一点尤为重要。卡芬太尼、瑞芬太尼和舒芬太尼是按照乌基法或七步法合成的，苄芬太尼是用齐格弗里德法生产的。样品经人体肝脏微粒体体外代谢后，采用气相色谱-质谱法（GC-MS）和液相色谱高分辨串联质谱法（LC-HRMS/MS）进行分析。采用匹配标准法和主成分分析法（PCA）找到了特征标记。在代谢后样本中发现了前体物质 4-ANBP、苯胺和 N-苯基乙酰胺以及几种代谢物，这表明体外代谢后仍保留了特定的合成信息。检测到的水平与案例研究中报告的浓度相符。此外，还采用了 LDA 方法，以最大限度地区分不同的合成方法，并确定似然比（LRs）。校准的 LR 值在 0.083 到 16 之间，假阳性和假阴性错误率非常低。总之，这项工作证明了结合化学特征分析和回顾性生物标志物分析来获取有关合成方法信息的可能性，这对法医重建和归属调查非常有用。

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来源期刊

Forensic Chemistry CHEMISTRY, ANALYTICAL-

CiteScore

5.70

自引率

14.80%

发文量

审稿时长

46 days

期刊介绍： Forensic Chemistry publishes high quality manuscripts focusing on the theory, research and application of any chemical science to forensic analysis. The scope of the journal includes fundamental advancements that result in a better understanding of the evidentiary significance derived from the physical and chemical analysis of materials. The scope of Forensic Chemistry will also include the application and or development of any molecular and atomic spectrochemical technique, electrochemical techniques, sensors, surface characterization techniques, mass spectrometry, nuclear magnetic resonance, chemometrics and statistics, and separation sciences (e.g. chromatography) that provide insight into the forensic analysis of materials. Evidential topics of interest to the journal include, but are not limited to, fingerprint analysis, drug analysis, ignitable liquid residue analysis, explosives detection and analysis, the characterization and comparison of trace evidence (glass, fibers, paints and polymers, tapes, soils and other materials), ink and paper analysis, gunshot residue analysis, synthetic pathways for drugs, toxicology and the analysis and chemistry associated with the components of fingermarks. The journal is particularly interested in receiving manuscripts that report advances in the forensic interpretation of chemical evidence. Technology Readiness Level: When submitting an article to Forensic Chemistry, all authors will be asked to self-assign a Technology Readiness Level (TRL) to their article. The purpose of the TRL system is to help readers understand the level of maturity of an idea or method, to help track the evolution of readiness of a given technique or method, and to help filter published articles by the expected ease of implementation in an operation setting within a crime lab.