Analysis of lipids using 2,4,6-trihydroxyacetophenone as a matrix for MALDI mass spectrometry

Lipids exhibit a broad range of chemical properties that make their analysis quite demanding. Today, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) represents a versatile tool in the field of lipid analysis, also offering the possibility for molecular structural identification using novel MALDI tandem time-of-flight (TOF/TOF) instrumentation. In this study, we evaluated 2,4,6-trihydroxyacetophenone (THAP) for the analysis of various lipid classes including neutral storage lipids (triacylglycerols), polar membrane lipids (glycerophospho- and sphingolipids), and glycosphingolipids. THAP proved to be a versatile matrix for the routine analysis of various lipids from biological samples (lipidomics). A sample preparation methodology was established using selective alkali salt doping for subsequent MS/MS experiments. Sodiated and lithiated molecules provided superior structural information on lipids (i.e., acyl group identification); thus, following this approach, both selective peak detection with high sensitivity and more reliable structural information were obtained simultaneously.