Identification of intact lipid peroxides by Ag+ coordination ion-spray mass spectrometry (CIS-MS).

Free radical-induced autoxidation of lipids containing polyunsaturated fatty acids (PUFA) has been implicated in numerous human diseases including atherosclerosis, neurodegenerative diseases, and cancer. Autoxidation of PUFAs generates hydroperoxides as primary oxidation products and further oxidation leads to cyclic peroxides as secondary oxidation products. It is challenging to identify these peroxides by conventional electro-spray ionization (ESI) mass spectrometry (MS) method because of their thermal and chemical instability under most analytical conditions. Ag(+) coordination ion-spray CIS-MS has proven to be a powerful tool to analyze these intact lipid peroxides. Ag(+) preferentially complexes with the double bonds and induces characteristic fragmentation in the gas phase. Monocyclic peroxides, bicyclic endoperoxides, serial cyclic peroxides, and dioxolane-isoprostane peroxides have been identified from the oxidation of cholesteryl arachidonate and phospholipids containing arachidonate. This technique has been widely used for structural identification but it is difficult to make it a quantitative tool because of the formation of multiple silver adducts.