DBDA matrix increases ion abundance of fatty acids and sulfatides in MALDI-TOF and mass spectrometry imaging studies

Abstract

MALDI-TOF MS is a powerful tool to analyze biomolecules owing to its soft ionization nature and generally results in simple spectra of singly charged ions. Moreover, implementation of the technology in imaging mode provides a means to spatially map analytes in situ. Recently, a new matrix, DBDA (N1,N4-dibenzylidenebenzene-1,4-diamine) was reported to facilitate the ionization of free fatty acids in the negative ion mode. Building on this finding, we sought to implement DBDA for MALDI mass spectrometry imaging studies in brain tissue and successfully map oleic acid, palmitic acid, stearic acid, docosahexaenoic acid and arachidonic acid using mouse brain sections. Moreover, we hypothesized that DBDA would provide superior ionization for sulfatides, a class of sulfolipids, with multiple biological functions. Herein we also demonstrate that DBDA is ideal for MALDI mass spectrometry imaging of fatty acids and sulfatides in brain tissue sections. Additionally, we show enhanced ionization of sulfatides using DBDA compared to three different traditionally used MALDI matrices. Together these results provide new opportunities for studies to measure sulfatides by MALDI-TOF MS including in imaging modes.

Development of benzimidazole derivatives as efficient matrices for the analysis of acidic small‐molecule compounds using matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry in negative ion mode

“…27 In addition, 1,5-naphthalenediamine (DAN) 28 and norharmane 29 for lipid analysis, 2-mercaptobenzothiazole (2-MBT) 30 for the analysis of phospholipids and 3-aminoquinoline (3AQ) 31 for oligosaccharide structure analysis are also popular. To meet the need for a wider range of analyte detection methods, as well as to obtain higher sensitivity and fewer interfering ions, other new matrices purposely designed for negative ion MALDI-MS analysis of small molecules, such as N-(1-naphthyl) ethylenediamine (NEDN), 32 N1, N4-dibenzyldiphenyl-1,4-diamine (DBDA) 33,34 and 4-dimethylaminobenzaldehyde (DMABA), 35 have been described, but they usually have certain application limitations. A significant breakthrough in this field was the introduction of 'proton sponges' as MALDI matrices.…”