High-Precision Mass Spectrometry of Lipids Using a Novel Ion Dissociation Technique (OAD)

Abstract

Lipids play essential roles in membrane structure, signal transduction, and energy storage, and their structural diversity often depends on the number and positions of carbon–carbon double bonds (C=C). Precise identification of C=C positions is crucial for understanding lipid function and its relationship to diseases. However, conventional low-energy collision-induced dissociation (CID) provides limited information on C=C positions. To overcome this limitation, we developed a novel ion dissociation technique termed oxygen attachment dissociation (OAD), which employs neutral atomic oxygen and hydroxyl radicals to selectively cleave at C=C sites without altering the ion charge state. When coupled with a Q-TOF mass spectrometer, OAD enables sensitive and selective analysis of intact lipids, allowing for both structural elucidation and quantitative profiling of lipid isomers. Applications to human plasma demonstrated the ability to discriminate C=C positional isomers with excellent linearity and reproducibility. OAD is expected to become a powerful tool for lipidomics and biomedical research.