Review of the applicability of ionic liquid matrices for the quantification of small molecules by MALDI MS

Abstract Ionic liquid matrices (ILMs) were introduced almost 20 years ago as alternatives to crystal matrices for MALDI MS analysis. They are protic ionic liquids synthesized by mixing conventional acidic MALDI matrices with an equimolar number of organic amines. They have certain advantageous attributes, such as: i. high homogeneity of the matrix + sample mixture, which increases the shot-to-shot reproducibility, ii. reducing the background on mass spectra, which is why molecules with low masses can be analyzed, and iii. the possibility of the quantitative analysis of small molecules. This review aims to present updated reports on the applicability of ILMs for the quantification of small molecules, and to critically discuss the features therein. The number of reports presenting quantitative analysis using ILMs is relatively small, despite the wide range of synthesized ILMs. Various representatives of small peptides, amino acids, pharmaceuticals, drugs, oligosaccharides, alkaloids and toxins were analyzed using ILMs based on DHB and CHCA acids. Furthermore, ILMs were found to be applicable for the imaging and mapping of lipids and small peptides. Even relatively similar ILMs vary from one another due to their ionization potential (intensity of signals in positive and negative ion extraction mode, fragmentation rate, adduct formation). Currently, there are no guidelines for the selection of ILMs for a specific task, which would appear to be a milestone in the application of ILMs for MALDI MS.