目的: 探究高分辨环形离子淌度质谱(Cyclic IMS)检测套索多肽类复杂药物构象(拓扑异构体)的可行性及潜在应用。方法:以Mccj25及Rubrinodin套索多肽为药物分析模型,将2种化合物分别于0、50、80 ℃处理4 h,采用高分辨Cyclic IMS直接进样的方式对样品进行分离、检测。结果:2种模型药物在3个温度下呈现不同的拓扑结构变化,Mccj25在3个温度下构象未发生明显变化,具有较稳定的拓扑结构,而Rubrinodin在3个温度下构象发生了明显变化;采用Cyclic IMS中的环形淌度可精准识别复杂药物的折叠、解体等构象变化。结论:Cyclic IMS可对复杂药物的构象(拓扑异构体)进行精准分析,可识别药物微小的构象变化,方法可操作性强,重现性较好,准确度高,可用于复杂药物的构象测定及质量控制。
Abstract
Objective: To explore the feasibility and potential applications of high-resolution cyclic ion mobility separation mass spectrometry (Cyclic IMS) for detecting the conformations (topological isomers) of complex medicines. Methods: Using MccJ25 and Rubrinodin lasso peptides as models, the compounds were subjected to heat treatment at 0, 50, and 80 ℃ for 4 h, respectively. The samples were then directly injected for separation and detection using high-resolution Cyclic IMS. Results: The two model compounds exhibited different topological structural changes at three temperatures tested. MccJ25 showed no significant conformational changes and exhibited a relatively stable topological structure across all temperatures. In contrast, Rubrinodin demonstrated significant conformational changes at each temperature. The cyclic ion mobility cell in Cyclic IMS was able to accurately identify conformational changes, such as folding and unfolding, in the complex drugs. Conclusion: Cyclic IMS can precisely analyze the conformation (topological isomers) of complex drugs, detect small conformational changes, and offers strong operability, good reproducibility, and high accuracy. It holds potential for use in the conformational determination and quality control of complex drug molecules.
关键词
环形离子淌度质谱 /
套索多肽 /
构象分析 /
拓扑异构体 /
质谱成像 /
质量控制
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Key words
cyclic ion mobility mass spectrometry /
lasso peptides /
conformational analysis /
topological isomers /
mass spectrometry imaging /
quality control
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中图分类号：
R 917
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参考文献
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脚注
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基金
* 国家药品监督管理局化学药品质量研究与评价重点实验室学科建设基金项目(2023HYZX02);药品监管科学全国重点实验室基金项目(2023SKLDRS0109);国家药品监督管理局药品监督科学体系建设重点项目(RS2024H005)
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