3-Acetylpyridine On-Tissue Paternò–Büchi Derivatization Enabling High Coverage Lipid C═C Location-Resolved MS Imaging in Biological Tissues

作者：Yanyan Chen, Chengyi Xie, Xiaoxiao Wang, Guodong Cao, Yi Ru, Yuanyuan Song, Ashok Iyaswamy, Min Li, Jianing Wang, Zongwei Cai · 发表于：Analytical Chemistry · 年份：2022 · DOI：10.1021/acs.analchem.2c03089 · 被引用次数：35 · 研究领域：Metabolomics and Mass Spectrometry Studies、Mass Spectrometry Techniques and Applications、Cancer, Lipids, and Metabolism

Unsaturated lipids containing single or more carbon-carbon double bonds (C═C) within tissues are closely associated with various types of diseases. Mass spectrometry imaging (MSI) has been used to study the spatial distribution of lipid C═C location isomers in tissue sections. However, comprehensive characterization of lipid C═C location isomers using MSI remains challenging. Herein, we established an on-tissue charge-switching Paternò-Büchi (PB) derivatization method using 3-acetylpyridine (3-AP) as a reaction reagent, which can be used to detect and assign C═C location of glycerophospholipids (GPLs) as well as neutral lipids, such as fatty acids (FAs), under the same experimental workflow using matrix-assisted laser desorption/ionization (MALDI)-MSI. High coverage of mono- and poly-unsaturated C═C location isomers among various lipid classes including FA, phosphatidylcholine (PC), and sulfatide (SHexCer) in distinct regions of the mouse brain and kidney was visualized using MALDI-MS/MS imaging. This method has also been applied to map the spatial distribution of lipid C═C location isomers in the Alzheimer's disease (AD) mice model for the first time, which provides a new tool to study the relationships between the distribution of lipid structural diversity and neurodegenerative diseases.