The demand for clinical toxicology analytical methods for identifying drugs of abuse and medicinal drugs is steadily increasing. Structural elucidation of amino amide‐type local anesthetic drugs and their main metabolites by GC‐EI‐MS and LC‐ESI‐MS/MS is of great analytical challenge. These compounds exhibit only/mostly fragments/product ions representing the amine‐containing residue, while the aromatic amide moiety remains unidentified. This task becomes even more complicated when discrimination between positional isomers of such compounds is required. Here, we report the development of a derivatization procedure for the differentiation and structural elucidation of a mixture of local anesthetic drugs and their metabolites that possess tertiary and secondary amines in water and urine. A method based on two sequential “in‐vial” instantaneous derivatization processes at ambient temperature followed by LC‐ESI‐MS/MS analysis was developed. 2,2,2‐Trichloro‐1,1‐dimethylethyl chloroformate (TCDMECF) was utilized to selectively convert the secondary amines into their carbamate derivatives, followed by hydrogen peroxide addition to produce the corresponding tertiary amine oxides. The resulting derivatives exhibited rich fragmentation patterns, enabling improved structural elucidation of the original compounds. The developed method was successfully applied to the differentiation and structural elucidation of prilocaine and its four positional isomers, which all possess similar GC and LC retention times and four of them exhibit almost identical EI‐MS and ESI‐MS/MS spectra, enabling their structural elucidation in a single LC‐ESI‐MS/MS analysis. The developed technique is fast and simple and enables discrimination between isomers based on different diagnostic ions/fragmentation patterns.

中文翻译：

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LC-MS衍生化后氨基酰胺类局麻药及其主要代谢物在尿中的结构解析及其在丙胺卡因位置异构体之间的区分中的应用。

用于鉴别滥用药物和药用药物的临床毒理学分析方法的需求正在稳步增加。通过 GC-EI-MS 和 LC-ESI-MS/MS 对氨基酰胺类局部麻醉药物及其主要代谢物的结构解析具有很大的分析挑战。这些化合物仅/大部分表现出代表含胺残基的碎片/产物离子，而芳族酰胺部分仍未确定。当需要区分此类化合物的位置异构体时，这项任务变得更加复杂。在这里，我们报告了一种衍生化程序的开发，用于局部麻醉药物及其在水和尿液中具有叔胺和仲胺的代谢物的混合物的分化和结构解析。开发了一种基于环境温度下两个连续“小瓶”瞬时衍生过程随后进行 LC-ESI-MS/MS 分析的方法。2,2,2-三氯-1,1-二甲基乙基氯甲酸酯（TCDMECF）用于选择性地将仲胺转化为其氨基甲酸酯衍生物，然后加入过氧化氢以产生相应的叔胺氧化物。由此产生的衍生物表现出丰富的碎片模式，能够改进原始化合物的结构解析。所开发的方法成功应用于丙胺卡因及其四种位置异构体的区分和结构解析，它们都具有相似的 GC 和 LC 保留时间，其中四种表现出几乎相同的 EI-MS 和 ESI-MS/MS 光谱，在单次 LC-ESI-MS/MS 分析中实现其结构解析。开发的技术快速而简单，可以根据不同的诊断离子/碎片模式区分异构体。