Dimethoxytriadinylation LC-MS/MS of Novichok A-Series Degradation Products in Human Urine
Dimethoxytriadinylation LC-MS/MS of Novichok A-Series Degradation Products in Human Urine
复制标题
人尿液中 Novichok A 系列降解产物的二甲氧基三腺苷化 LC-MS/MS
DOI：
10.1021/acs.analchem.1c04634
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发表时间：
2022
影响因子：
7.4
通讯作者：
Manabu Tokeshi
中科院分区：
文献类型：
--
作者：
Akinori Yamaguchi;Hajime Miyaguchi;Manabu Tokeshi
Novichok A系列化合物是一种新型神经毒剂，对世界各地的公民构成越来越大的威胁;然而，尚未报告用于检测其水解产物的分析方法。在此，开发了一种筛选方法，使用液相色谱-串联质谱法（LC-MS/MS）检测和鉴定Novichok A系列降解产物（A230、A232、A234、A262和一种相关化合物的水解产物）和烷基甲基膦酸（RMPA，常规神经毒剂水解产物）。确定了合适的衍生化试剂4-（4，6-二甲氧基-1，3，5-三嗪-2-基）-4-甲基吗啉氯化物（DMTMM），并优化了反应条件。Novichok A系列降解产物的衍生酯稳定且易于检测。我们使用该衍生化实现了尿液中Novichok水解产物（0.40-4.0 ng/mL）的第一个分析方法。的RMPA（0.1-0.4纳克/毫升）的检测限与以前的报告中提出的涉及五氟苯甲基化或直接LC-MS/MS。新开发的方法的适用性进行了评估，通过分析尿样从禁化武组织第五次生物医学能力测试。
Novichok A-series compounds, novel nerve agents, pose an increasing threat to citizens worldwide; however, no analytical methods have been reported for detecting their hydrolysis products. Herein, a screening method was developed to detect and identify Novichok A-series degradation products (hydrolysates of A230, A232, A234, A262, and one related compound) and alkyl methylphosphonic acids (RMPAs, conventional nerve agent hydrolysates) using liquid chromatography–tandem mass spectrometry (LC–MS/MS). We identified a suitable derivatization reagent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM), and optimized the reaction conditions. The derivatized esters of Novichok A-series degradation products were stable and easily detected. We used this derivatization to achieve the first analytical method for Novichok hydrolysis products in urine (0.40–4.0 ng/mL). The detection limits of the RMPAs (0.1–0.4 ng/mL) were comparable to those presented in previous reports involving pentafluorobenzylation or direct LC–MS/MS. The applicability of the newly developed method was evaluated by analyzing urine samples from the OPCW Fifth Biomedical Proficiency Test.