Sun Dong, Wang Chunyu, Fan Yanxia, Gu Jingkai
Research Center for Drug Metabolism, School of Life Sciences, Jilin University, Changchun, 130012, China.
State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012, China.
J Pharm Anal. 2023 Jun;13(6):683-688. doi: 10.1016/j.jpha.2023.04.011. Epub 2023 Apr 21.
During the analysis of benziamidazole-class irreversible proton pump inhibitors, an unusual mass spectral response with the mass-to-charge ratio at [M+10] intrigued us, as it couldn't be assigned to any literature known relevant structure, intermediate or adduct ion. Moreover, this mysterious mass pattern of [M+10] has been gradually observed by series of marketed proton pump inhibitors, viz. omeprazole, pantoprazole, lansoprazole and rabeprazole. All the previous attempts to isolate the corresponding component were unsuccessful. The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate , which is the common fragment ion of series of labile aggregates. The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation. These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization. The structure of the corresponding pyridinium thiocyanate species of omeprazole () has been eventually characterized with the help of synthetic specimen (). Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance, chemical derivatization and colorimetric experiments.
在对苯并咪唑类不可逆质子泵抑制剂进行分析时，质荷比为[M + 10]的异常质谱响应引起了我们的兴趣，因为它无法归属于任何文献中已知的相关结构、中间体或加合离子。此外，一系列市售质子泵抑制剂，即奥美拉唑、泮托拉唑、兰索拉唑和雷贝拉唑，都逐渐观察到了这种神秘的[M + 10]质谱模式。此前所有分离相应成分的尝试均未成功。本研究工作将这种信号归因于硫氰酸吡啶质谱中间体，它是一系列不稳定聚集体的常见碎片离子。此类聚集体的起源可追溯到酸促降解形成的反应中间体。这些反应中间体倾向于相互反应，并通过电喷雾电离在水/乙腈溶液中系统地产生一系列复杂的聚集体。奥美拉唑（）相应硫氰酸吡啶物种的结构最终借助合成样品（）得以表征。我们的结构推测及其起源得到了原位核磁共振、化学衍生化和比色实验的支持。
