Mass spectrometry imaging is of growing interest for chemical mapping of lipids at the surface of tissue sections. Many efforts have been devoted to optimize matrix choice and deposition technique for positive ion mode analyses. The identification of lipid species desorbed from tissue sections in the negative mode can be significantly improved by using 9-aminoacridine together with a robust deposition method, yielding a superior signal-to-noise ratio and thus a better contrast for the ion images in comparison to classical matrices such as α-cyano-4-hydroxycinnamic acid, 2,5-dihydroxybenzoic acid, or 2,4,6-trihydroxyacetophenone. Twenty-eight different lipid species (phosphatidic acids, phosphatidylethanolamines, phosphatidylserines, phosphatidylglycerols, phosphatidylinositols, phosphatidylinositol-phosphates, and sulfatides) were scrutinized on rat brain tissue sections, and systematic MS/MS studies were conducted. It was possible to identify isobaric species differing by their fatty acid chains thanks to the improved sensitivity.

Mass spectrometry imaging of lipids using MALDI-TOF/TOF mass spectrometers is of growing interest for chemical mapping of organic compounds at the surface of tissue sections. Many efforts have been devoted to the best matrix choice and deposition technique. Nevertheless, the identification of lipid species desorbed from tissue sections remains problematic. It is now well-known that protonated, sodium- and potassium-cationized lipids are detected from biological samples, thus complicating the data analysis. A new sample preparation method is proposed, involving the use of lithium salts in the matrix solution in order to simplify the mass spectra with only lithium-cationized molecules instead of a mixture of various cationized species. Five different lithium salts were tested. Among them, lithium trifluoroacetate and lithium iodide merged the different lipid adducts into one single lithium-cationized species. An optimized sample preparation protocol demonstrated that the lithium trifluoroacetate salt slightly increased desorption of phosphatidylcholines. Mass spectrometry images acquired on rat brain tissue sections by adding lithium trifluoroacetate showed the best results in terms of image contrast. Moreover, more structurally relevant fragments were generated by tandem mass spectrometry when analyzing lithium-cationized species.