Analysis of degradation products of nerve agents in biological fluids by ion chromatography-tandem mass spectrometry.

IF 2.8 4区医学 Q2 TOXICOLOGY Forensic Toxicology Pub Date : 2023-01-01 DOI:10.1007/s11419-022-00633-x

Mai Otsuka, Hajime Miyaguchi

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引用次数: 2

Abstract

Purpose: The detection of hydrolysis products of nerve agents (alkyl methylphosphonic acids; RMPAs) in biological samples from victims is important to confirm exposure to nerve agents. However, analysis of RMPAs is difficult due to their high hydrophilicity. The aim of this study was to develop ion chromatography-tandem mass spectrometry (IC-MS/MS) methods using commercially available equipment and columns to analyze RMPAs in human urine and serum with high sensitivity and without using complicate techniques.

Methods: A Dionex IonPac AS11-HC anion-exchange column was used to analyze six RMPAs (MPA, EMPA, IMPA, ⁱBuMPA, CHMPA, and PMPA). For pretreatments of biological fluids, we developed two pretreatment methods (Method 1: dilution and ultrafiltration; Method 2: removal of chloride ions with Ag cartridges).

Results: Six RMPAs including highly hydrophilic methylphosphonic acid and ethyl methylphosphonic acid could be analyzed with sufficient retention times and peak shape. The detection limits of RMPAs were improved using Dionex OnGuard II Ba/Ag/H cartridges and MetaSEP IC-Ag cartridges (urine: 0.5-5 ng/mL; serum: 1-5 ng/mL). These methods were also applied to the test samples for the Organisation for the Prohibition of Chemical Weapons Biomedical Proficiency Tests.

Conclusions: RMPAs could be sufficiently analyzed by IC-MS/MS. In addition, the limits of detection were superior to those obtained in our previous study involving LC-MS/MS or derivatization-LC-MS/MS method. For analysis of biological samples, an appropriate pretreatment method can be chosen according to the amount of sample available for analysis and expected RMPA concentrations.

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离子色谱-串联质谱法分析生物体液中神经毒剂降解产物。

目的:检测神经毒剂(烷基甲基膦酸)水解产物;受害者生物样本中的RMPAs对于确认神经毒剂暴露非常重要。然而，由于RMPAs的高亲水性，分析起来很困难。本研究的目的是建立离子色谱-串联质谱(IC-MS/MS)方法，使用市售设备和色谱柱分析人体尿液和血清中的RMPAs，灵敏度高，无需复杂的技术。方法:采用Dionex IonPac AS11-HC阴离子交换柱对6种rmpa (MPA、EMPA、IMPA、iBuMPA、CHMPA、PMPA)进行分析。对于生物流体的预处理，我们开发了两种预处理方法(方法一:稀释和超滤;方法二:用银筒去除氯离子)。结果:高亲水性甲基膦酸和乙基甲基膦酸6种RMPAs均可分析，保留时间和峰形均足够。采用Dionex OnGuard II Ba/Ag/H试剂盒和MetaSEP IC-Ag试剂盒提高RMPAs的检出限(尿:0.5 ~ 5 ng/mL;血清:1-5 ng/mL)。这些方法也适用于禁止化学武器组织生物医学能力测试的测试样本。结论:IC-MS/MS能充分分析RMPAs。此外，该方法的检出限优于我们之前的LC-MS/MS或衍生化-LC-MS/MS方法。对于生物样品的分析，可根据可供分析的样品数量和预期RMPA浓度选择合适的预处理方法。

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来源期刊

Forensic Toxicology TOXICOLOGY-

CiteScore

5.80

自引率

9.10%

发文量

审稿时长

3 months

期刊介绍： The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published. Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).