Development of an Efficient On-Tissue Epoxidation Reaction Mediated by Urea Hydrogen Peroxide for MALDI MS/MS Imaging of Lipid C═C Location Isomers

Unsaturated lipids containing different numbers and locations of C═C bonds are significantly associated with a variety of cellular and metabolic functions. Although matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has been used to visualize the spatial distribution patterns of various lipids in biological tissues, in situ identification, discrimination, and visualization of lipid C═C location isomers remain challenging. Herein, an efficient and fast on-tissue chemical derivatization (OTCD) approach was developed to pinpoint the locations of C═C bonds in complex lipids in situ via methyltrioxorhenium (MTO)-catalyzed epoxidation of C═C with a urea hydrogen peroxide (UHP)/hexafluoroisopropanol (HFIP) system. The efficiency of OTCD could reach 100% via one-step spray deposition of the solution mixture of MTO/UHP/HFIP at room temperature. The developed OTCD method provided rich structural information on lipid C═C location isomers, and their accurate spatial distribution patterns were resolved in mouse brain tissues. Tissue-specific distributions and changes of lipid C═C location isomers in the liver sections of obese ob/ob and diabetic db/db mice were further investigated, and their correlation in two animal models was revealed. The simplicity and high efficiency of the OTCD method developed for MALDI tandem MSI of lipid C═C location isomers possess great potential for functional spatial lipidomics.