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.
ZHU Shao-zhou
,
FAN Li-jiao
,
ZHANG Tuo
,
SUN Jia-bei
,
YAO Jing
,
HUANG Hai-wei
,
ZHANG Qing-sheng
. Application of cyclic ion mobility mass spectrometry for conformational analysis of lasso peptide-type complex drugs*[J]. Chinese Journal of Pharmaceutical Analysis, 2024
, 44(11)
: 1997
-2003
.
DOI: 10.16155/j.0254-1793.2024-0112
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