MALDI‐MS Analysis of Carbohydrates Using Ionic Liquid Matrices: Insights Into Ionization Efficiency and Sample Homogeneity

Since the introduction of ionic liquids matrices (ILMs) in MALDI-MS, they have demonstrated several advantages over crystalline matrices, including improved desorption/ionization efficiency and enhanced sample optical homogeneity. This study explored among them, specific ionic solid matrices (ISMs) and non-ionic solid matrices (NISMs) for low molecular weight (LMW) carbohydrate analysis. The investigation involved modifying the cationic components of the acid-amine mixtures with various aliphatic amines, such as ethylamine (EAM), ethanolamine (EOHAM), triethylamine (TEAM), n-butylamine (BAM), butanolamine (BOHAM), and tributylamine (TBAM), derived from classical acidic MALDI matrices (E-α-cyano-4-hydroxycinnamic acid (ECHCA), E-sinapinic acid (ESA), and Z-sinapinic acid (ZSA)). The physical and morphological properties of the proposed mixed matrices were analyzed. MALDI mass spectrometry imaging (MSI) was used to assess analyte distribution homogeneity. UV-Vis absorption and diffuse reflectance, ¹H-NMR, and LDI-MS techniques were employed to characterize matrix ionicity. The results indicate that the efficiency of MALDI matrices is independent of their ionic character, while the difference in desorption/ionization efficiency observed in acid-amine matrices may depend on the proximity of ionizable groups in the solid state, suggesting the generation of a new chromophoric unit with more suitable physicochemical properties for the MALDI matrix function. The heterogeneity observed in all samples underscores the challenges in obtaining reproducible data within the same spot or analytical replicates.