Reactive Matrices for MALDI-MS of Cholesterol

Anal Chem. 2023 Nov 21;95(46):16786-16790. doi: 10.1021/acs.analchem.3c04127. Epub 2023 Nov 10.


Cholesterol is a critical molecule whose dysregulation in certain brain regions is related to multiple neurological disorders. It is of pathological importance to map the distribution of cholesterol in brain. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been widely used in the molecular imaging of metabolites at a high spatial resolution. However, it is challenging to analyze cholesterol by MALDI-MS due to its difficulty in ionization. Herein, we present for the first time a type of reactive matrix for MALDI-MS of cholesterol. Methylpyridinium carboxaldehydes react with cholesterol and other hydroxyl-containing sterols, which greatly enhanced both desorption and ionization and improved the limits of detection to the low μg/mL range. Compared with previous methods, our reactive matrix requires only one step of chemical derivatization and avoids time-consuming enzymatic reaction, which simplified the sample pretreatment. The reactive matrix was successfully used in mapping the distribution of cholesterol in brain tissue sections using MALDI-MS imaging. In summary, this work has provided a sensitive and simple method for the MALDI-MS analysis of cholesterol, has proposed a novel solution to visualize the distribution of sterol metabolites, and has great potential for applications in neurological and pathological studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain
  • Cholesterol
  • Phytosterols*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Sterols*


  • Sterols
  • Cholesterol
  • Phytosterols