Online photochemical derivatization enables comprehensive mass spectrometric analysis of unsaturated phospholipid isomers

• Published in: Nature communications Vol. 10; no. 1; p. 79
• Main Authors: Zhang, Wenpeng, Zhang, Donghui, Chen, Qinhua, Wu, Junhan, Ouyang, Zheng, Xia, Yu
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.01.2019; Nature Publishing Group UK; Nature Portfolio
• Subjects: Biomarkers; Breast cancer; Carbon; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Internet; Ions; Isomers; Lipids; Liquid chromatography; Liver; Localization; Mass spectrometry; Mass spectroscopy; Phospholipids; Photochemicals; Scientific imaging; Spectroscopy; Structural analysis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07963-8

Mass spectrometry-based lipidomics is the primary tool for the structural analysis of lipids but the effective localization of carbon-carbon double bonds (C=C) in unsaturated lipids to distinguish C=C location isomers remains challenging. Here, we develop a large-scale lipid analysis platform by coupling online C=C derivatization through the Paternò-Büchi reaction with liquid chromatography-tandem mass spectrometry. This provides rich information on lipid C=C location isomers, revealing C=C locations for more than 200 unsaturated glycerophospholipids in bovine liver among which we identify 55 groups of C=C location isomers. By analyzing tissue samples of patients with breast cancer and type 2 diabetes plasma samples, we find that the ratios of C=C isomers are much less affected by interpersonal variations than their individual abundances, suggesting that isomer ratios may be used for the discovery of lipid biomarkers.