Lipid Isobaric Mass Tags via Aziridination for Probing Isomeric Structures and Accurate Quantification

Unsaturated lipids constitute a dominant portion of lipids in mammalian cells and often exist as a mixture of isomers. Knowing concentrations of lipids is essential for understanding their functions in physiology and diseases. Herein, a novel aziridination-based isobaric tag labeling strategy is developed for isomeric characterization and accurate quantification of unsaturated lipids. This strategy allows (i) determination of lipid double bond positional isomers, (ii) quantification of unsaturated lipids and lipid isomers, and (iii) improvement of ionization efficiencies of nonpolar lipids. The power of the method has been demonstrated in characterization and quantification of various categories of lipids such as fatty acids, phosphoglycerol lipids, cholesteryl esters and glycerides. Remarkably, 13 CE lipid isomers were identified and simultaneously quantified from human plasma without requiring the use of lipid standards.