Pyrylium-Based Derivatization for Rapid Labeling and Enhanced Detection of Cholesterol in Mass Spectrometry Imaging

Shuai Huang, Xinxin Liu, Dan Liu, Xiaozhe Zhang, Lihua Zhang, Weidong Le, Yukui Zhang

Research output: Contribution to journalArticlepeer-review


Cholesterol in the central nervous system has been increasingly found to be closely related to neurodegenerative diseases. Defects in cholesterol metabolism can cause structural and functional disorders of the central nervous system. The detection of abnormal cholesterol is of great significance for the cognition of physiological and pathological states of organisms, and the spatial distribution of cholesterol can also provide more clues for our understanding of the complex mechanism of disease. Here, we developed a novel pyrylium-based derivatization reagent combined with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to visualize cholesterol in biological tissues. A new class of charged hydroxyl derivatization reagents was designed and synthesized, and finally 1-(carboxymethyl)-2,4,6-trimethylpyridinium (CTMP) was screened for tissue derivatization of cholesterol. Different from the shortcomings of traditional hydroxyl labeling methods such as harsh reaction conditions and long reaction time, in our study, we combined the advantages of CTMP itself and the EDCl/HOBt reaction system to achieve instant labeling of cholesterol on tissues through two-step activation. In addition, we also reported changes in cholesterol content in different stages and different brain regions during disease development in SOD1 mutant mouse model. The cholesterol derivatization method we developed provides an efficient way to explore the distribution and spatial metabolic network of cholesterol in biological tissues.

Original languageEnglish (US)
Pages (from-to)2310-2318
Number of pages9
JournalJournal of the American Society for Mass Spectrometry
Issue number12
StatePublished - Dec 7 2022

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy


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