Natural Antioxidant-Derived Compounds and Materials as Emerging MALDI Matrices: Applications, Evidence, and...

Antioxidants constitute a chemically diverse group of compounds that are widely studied in food, natural products, and biological systems, creating a continuing need for analytical methods capable of their reliable characterization. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides rapid molecular analysis with minimal sample preparation and has been increasingly applied to low-molecular-weight compounds, natural products, food constituents, and biological samples. However, the analysis of small molecules by MALDI-MS is often limited by matrix-derived background signals, differences in ionization efficiency, heterogeneous crystallization, and difficulties in achieving reliable quantitative measurements, highlighting the need for alternative matrix systems with improved and more controllable analytical properties. In this context, naturally occurring antioxidants are of particular interest because many possess aromatic and conjugated structures, UV-absorbing groups, acid-base and redox properties, and functional groups capable of matrix-analyte interactions, which may support their function as MALDI matrices. This review summarizes the use of MALDI-MS for the analysis of antioxidant compounds in purified samples, plant extracts, food products, and biological materials, while critically evaluating the emerging concept of using naturally occurring antioxidants as alternative MALDI matrices. Particular emphasis is placed on the structural and physicochemical features relevant to matrix performance, including aromaticity, UV absorption, acid-base properties, redox behavior, crystallization, and matrix-analyte interactions. Conventional organic matrices are discussed alongside emerging alternatives, including ionic liquid matrices, nanomaterial-based systems, carbon-based materials, and matrix-free approaches. Importantly, the available evidence indicates that only a limited number of natural antioxidant-derived compounds and materials have been experimentally demonstrated as MALDI matrices, whereas evidence for other candidates remains preliminary or theoretical. Their potential analytical value is further considered in relation to reproducibility, background interference, matrix selectivity, and quantitative performance, together with future opportunities involving rational matrix design, mass spectrometry imaging, and computational approaches. Natural antioxidant-derived compounds and materials therefore represent an emerging and still insufficiently explored class of MALDI matrices that could expand the range of matrix chemistries available for small-molecule analysis, although their analytical value will ultimately depend on compound-specific experimental validation rather than antioxidant activity alone.