1H-pteridine-2,4-dione (lumazine): a new MALDI matrix for complex (phospho)lipid mixtures analysis

Nowadays, matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry represents an emerging and versatile tool for analysis of lipids. However, direct (i.e., with no previous separation of lipid classes) analysis of crude extracts containing a complex mixture of lipids (a problem typically encountered in shotgun lipidomics) is still a quite challenging task using a conventional MALDI matrix such as 2,5-dihydroxybenzoic acid (DHB). Indeed, in the presence of phospholipids containing quaternary ammonium groups, such as phosphatidylcholines and sphingomyelins, strong ionization-suppression effects are experienced especially in positive ion mode. To overcome this limitation, lumazine (1H-pteridine-2,4-dione) was evaluated as an alternative matrix. Lumazine in the solid state showed an absorption maximum at 350 nm, ionizes/desorbs without appreciable decomposition and extensive cluster formation, and can be used in both ion modes. In positive ion mode, the main species were M(*+) and 2M(*+) radical cations and cationized species ([M+H](+), [M+Na](+), [M+2Na+2Li-3H](+)). In negative ion mode, the main signals observed were the deprotonated molecular ion and the radical anion. The signal-to-noise ratio for phosphatidylglycerols and phosphatidylethanolamines using lumazine was almost 1 order of magnitude higher than that observed for DHB. Lumazine was successfully used for MALDI analysis (positive and negative ion modes) of crude lipid extracts of milk, soymilk, and hen egg, where phosphatidylethanolamines, phosphatidylserines, and phosphatidylinositols could additionally be detected.