A sensitive method for simultaneous screening exposure to 14 alkylating agents based on tripeptide adducts: an efficient approach for chemical weapon verification and chemical impurity profiling in plasma samples

IF 3.8 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Analytical and Bioanalytical Chemistry Pub Date : 2025-04-17 DOI:10.1007/s00216-025-05870-8

Bo Chen, Deshen Liang, Huilan Yu, Changcai Liu, Ling Yuan, Fengyun Wang, Shilei Liu

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引用次数: 0

Abstract

For the implementation of the Chemical Weapons Convention, the Organisation for Prohibition of Chemical Weapons (OPCW) designates laboratories for the analysis of chemicals that can be used as chemical warfare agents (CWAs). In these laboratories, analytical methods for detecting CWAs have been developed for environmental and biomedical samples. Protein adducts from exposed biomedical samples are an important type of biomarker for verification of their abuse. Moreover, these adducts could also be applied in chemical impurity profiling studies of biomedical samples. Alkylating agents, as cytotoxicants, can react with Cys³⁴ in human serum albumin, and cysteine-proline-phenylalanine (CPF) tripeptide adducts generated from proteinase K digestion of modified albumin have been used as biomarkers for retrospective detection of exposure to sulfur mustards or nitrogen mustards. In this study, a sensitive screening method for detecting exposure to 14 alkylating agents in one analytical run was established through sample preparation and instrumental detection optimization. Ultrahigh-performance liquid chromatography–triple quadrupole mass spectrometry (UHPLC–TQ MS) operated in multiple reaction monitoring (MRM) mode and combined with an optimized chromatographic program was used for detecting the 14 corresponding CPF tripeptide adducts. The limits of detection (LODs) are in the range of 0.200–10.0 ng/mL exposure concentrations in human plasma. This method could also allow impurity profiling applicable for potential attribution of sulfur and nitrogen mustard in plasma through retrospective analysis of exposed biomedical samples with impurity compositions as low as 0.1%. This method has potential in clinical diagnosis, CWA verification and forensic identification applications.

Graphical Abstract

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同时筛选14种基于三肽加合物的烷基化剂的灵敏方法：一种有效的化学武器核查和血浆样品化学杂质分析方法。

为了执行《化学武器公约》，禁止化学武器组织（禁化武组织）指定了实验室来分析可用作化学战剂的化学品。在这些实验室中，为环境和生物医学样品开发了检测CWAs的分析方法。暴露的生物医学样品中的蛋白质加合物是验证其滥用的重要生物标志物。此外，这些加合物还可用于生物医学样品的化学杂质分析研究。烷基化剂作为细胞毒物可与人血清白蛋白中的Cys34发生反应，改性白蛋白在蛋白酶K消化过程中产生的半胱氨酸-脯氨酸-苯丙氨酸（CPF）三肽加合物已被用作硫芥菜或氮芥菜暴露回顾性检测的生物标志物。本研究通过样品制备和仪器检测优化，建立了一次检测14种烷基化剂暴露的灵敏筛选方法。采用超高效液相色谱-三重四极杆质谱（UHPLC-TQ MS）多反应监测（MRM）模式，结合优化的色谱程序对14种相应的CPF三肽加合物进行检测。检测限（lod）范围为0.200-10.0纳克/毫升暴露浓度在人血浆中。该方法还可以通过对杂质成分低至0.1%的暴露生物医学样品进行回顾性分析，实现适用于血浆中硫和氮芥潜在归属的杂质分析。该方法在临床诊断、超声心动图验证和法医鉴定等方面具有潜在的应用价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Analytical and Bioanalytical Chemistry 化学-分析化学

CiteScore

8.00

自引率

4.70%

发文量

638

审稿时长

2.1 months

期刊介绍： Analytical and Bioanalytical Chemistry’s mission is the rapid publication of excellent and high-impact research articles on fundamental and applied topics of analytical and bioanalytical measurement science. Its scope is broad, and ranges from novel measurement platforms and their characterization to multidisciplinary approaches that effectively address important scientific problems. The Editors encourage submissions presenting innovative analytical research in concept, instrumentation, methods, and/or applications, including: mass spectrometry, spectroscopy, and electroanalysis; advanced separations; analytical strategies in “-omics” and imaging, bioanalysis, and sampling; miniaturized devices, medical diagnostics, sensors; analytical characterization of nano- and biomaterials; chemometrics and advanced data analysis.