Gas chromatography negative chemical ionization mass spectrometry (GC-NCI-MS) is a preferred instrumental approach for the trace and ultra-trace analysis of various toxic organics and their metabolites in human biological fluids. Specifically, the method has played an important role in the highly sensitive and specific quantitative detection of persistent highly halogenated compounds in environmental matrices and biota during the past few decades. However, for the analysis of toxic metabolites with active hydrogen atoms, such as acids, alcohols, and phenolic compounds, from biological matrixes or organics without electronegative atoms or groups, a derivatization step is often needed prior to GC analysis. Such derivatization aims to change the properties of targets to improve their separation, increase their volatility, and enhance the sensitivity of instrumental detection. This review summarizes three derivatization strategies commonly used for GC methods, i.e., alkylation, silylation, and acylation, together with their application combined with GC-NCI-MS for the high sensitivity analysis of toxic organic metabolites in the human body. The advantages and disadvantages of each derivatization method and potential directions for future applications are discussed. Given the broad variety of applications as well as the compound-specific sensitivity for the ultra-trace analysis of target xenobiotics in human biological fluids, subsequent studies are required to develop convenient, faster derivatization procedures and reagents better suited for routine analysis.

Graphical abstract

气相色谱负化学电离质谱 (GC-NCI-MS) 是对人体生物体液中各种有毒有机物及其代谢物进行痕量和超痕量分析的首选仪器方法。具体而言，该方法在过去几十年中在环境基质和生物群中持久性高卤化化合物的高灵敏度和特异性定量检测中发挥了重要作用。然而，对于来自生物基质或有机物的活性氢原子的有毒代谢物（如酸、醇和酚类化合物）的分析，通常需要在 GC 分析之前进行衍生化步骤。这种衍生化旨在改变目标的性质，以改善它们的分离，增加它们的挥发性，并提高仪器检测的灵敏度。本综述总结了 GC 方法常用的三种衍生化策略，即烷基化、硅烷化和酰化，以及它们与 GC-NCI-MS 相结合在人体内有毒有机代谢物的高灵敏度分析中的应用。讨论了每种衍生方法的优缺点以及未来应用的潜在方向。鉴于人类生物体液中目标异生素超痕量分析的广泛应用以及化合物特异性敏感性，后续研究需要开发方便、快速的衍生化程序和更适合常规分析的试剂。本综述总结了 GC 方法常用的三种衍生化策略，即烷基化、硅烷化和酰化，以及它们与 GC-NCI-MS 相结合在人体内有毒有机代谢物的高灵敏度分析中的应用。讨论了每种衍生方法的优缺点以及未来应用的潜在方向。鉴于人类生物体液中目标异生素超痕量分析的广泛应用以及化合物特异性敏感性，后续研究需要开发方便、快速的衍生化程序和更适合常规分析的试剂。本综述总结了 GC 方法常用的三种衍生化策略，即烷基化、硅烷化和酰化，以及它们与 GC-NCI-MS 相结合在人体内有毒有机代谢物的高灵敏度分析中的应用。讨论了每种衍生方法的优缺点以及未来应用的潜在方向。鉴于人类生物体液中目标异生素超痕量分析的广泛应用以及化合物特异性敏感性，后续研究需要开发更适合常规分析的方便、更快的衍生化程序和试剂。连同它们的应用，结合 GC-NCI-MS 对人体内有毒有机代谢物进行高灵敏度分析。讨论了每种衍生方法的优缺点以及未来应用的潜在方向。鉴于人类生物体液中目标异生素超痕量分析的广泛应用以及化合物特异性敏感性，后续研究需要开发方便、快速的衍生化程序和更适合常规分析的试剂。连同它们的应用，结合 GC-NCI-MS 对人体内有毒有机代谢物进行高灵敏度分析。讨论了每种衍生方法的优缺点以及未来应用的潜在方向。鉴于人类生物体液中目标异生素超痕量分析的广泛应用以及化合物特异性敏感性，后续研究需要开发方便、快速的衍生化程序和更适合常规分析的试剂。

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