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Lipid profiling is a key element of modern biology and medicine, providing information on the structure, function, and dynamics of lipid metabolism in health and disease. This review presents the latest state of the art in the application of matrix-assisted laser ionization mass spectrometry (MALDI-MS) in lipidomics, with a particular focus on the analysis of cholesterol, triglycerides (TAGs), and the main classes of phospholipids and sphingolipids. The theoretical basis of the technique is discussed, including ionization mechanisms, matrix selection and mass analyzer configurations, and the influence of experimental parameters on spectral quality. The specificity of sterol and TAG ionization, challenges associated with ion suppression, and strategies for improving detection sensitivity and selectivity are discussed. Particular attention is paid to molecular imaging (MALDI-MSI), which enables spatial mapping of lipids in tissues and is of increasing importance in neurobiological, oncological, and metabolic research. The review highlights the advantages of MALDI for rapid lipid profiling and tissue analysis, while also pointing out technical limitations (e.g., difficulties in detecting sterols, matrix interference, limited quantification) and the need for method standardization. MALDI-MS appears to be a complementary technique to LC-MS/ESI-MS and DESI-MS, with great translational potential, particularly in the context of diagnostics, biomarker studies, and in situ lipid imaging.
Aebisher et al. (Fri,) studied this question.