MALDI matrices for low molecular weight compounds: an endless story?

Abstract

Since its introduction in the 1980s, matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has gained a prominent role in the analysis of high molecular weight biomolecules such as proteins, peptides, oligonucleotides, and polysaccharides. Its application to low molecular weight compounds has remained for long time challenging due to the spectral interferences produced by conventional organic matrices in the low m/z window. To overcome this problem, specific sample preparation such as analyte/matrix derivatization, addition of dopants, or sophisticated deposition technique especially useful for imaging experiments, have been proposed. Alternative approaches based on second generation (rationally designed) organic matrices, ionic liquids, and inorganic matrices, including metallic nanoparticles, have been the object of intense and continuous research efforts. Definite evidences are now provided that MALDI MS represents a powerful and invaluable analytical tool also for small molecules, including their quantification, thus opening new, exciting applications in metabolomics and imaging mass spectrometry. This review is intended to offer a concise critical overview of the most recent achievements about MALDI matrices capable of specifically address the challenging issue of small molecules analysis. Graphical abstract An ideal Book of matrices for MALDI MS of small molecules.

Carbon‐Based Fingerprint Powder as a One‐Step Development and Matrix Application for High‐Resolution Mass Spectrometry Imaging of Latent Fingerprints

“…This pattern of carbon clusters is very similar to that of colloidal graphite reported by Yagnik et al (see supplementary information of the reference), suggesting CFP might be mostly made of graphite particles (25). It is worth noting that CHCA also suffers from matrix contamination of the low mass range, although to a lesser extent (28). Large molecules, such as TGs and diacylglycerols (DGs), are well separated from low mass carbon clusters and clearly visible in the positive mode mass spectrum ( Fig.…”

Characterization of bioactive and nutraceutical compounds occurring in olive oil processing wastes

“…However, the success of a MALDI‐MS examination, especially for LMW compounds, is strongly related to the matrix used that should be able to favor analyte ionization without or with negligible matrix interference. Because of the well‐known advantages for improving intra‐spot and spot‐to‐spot repeatability, higher sensitivity at lower laser fluences, and reduced fragmentations, the use of binary matrices for MALDI analysis is commonly reported in the literature .…”

“…One of the first binary components tested was 1,8‐bis(dimethylamino)naphthalene (DMAN), called also “proton sponge”, a strongly basic matrix (pK BH+ value of 18 in acetonitrile (ACN)), which allows the proton extraction from very weak acids even in the liquid phase . Since DMAN was reported to be unstable under high vacuum conditions, leading to variable matrix‐to‐analyte ratio and contamination of the mass spectrometer ion optics, novel proton sponges were suggested to overcome this issue . Among them TMGN (1,8‐bis(tetramethylguanidino)naphthalene) is a possible candidate being a commercial proton sponge matrix (pK BH+ = 25.1 in ACN) first proposed for the determination of perfluorinated compounds in water samples .…”

norHarmane containing ionic liquid matrices for low molecular weight MALDI‐MS carbohydrate analysis: The perfect couple with α‐cyano‐4‐hydroxycinnamic acid

“…The region of their m/z values is the region where classical crystalline matrices show not only the molecular ions but abundant signals with different origin (ie, fragments from molecular ions; clusters; fragments from clusters), too. The different efforts conducted in order to overcome this experimental problem are described in detail in the recent Calvano's review . The same topic is also discussed in U. Bahr and T. W. Jaskolla review on Employing “Second Generation” Matrices .…”

“…The same topic is also discussed in U. Bahr and T. W. Jaskolla review on Employing “Second Generation” Matrices . In the case of CHCA, several matrix‐related ions are generated together with sodiated and potassiated adducts covering the m/z range up to 1300 (eg, m/z 1287 ([5 M + 4 K‐3H] + )).…”