A novel matrix of isoliquiritigenin (ISL), a flavonoid with a chalcone structure (4,2',4'-trihydroxychalcone), was demonstrated to be advantageous in the analysis of neutral oligosaccharides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). With ISL as a matrix, adequate signal for an analyte can be obtained in much lower matrix concentrations and laser intensity compared to commonly used MALDI matrices. Four different sample preparation methods were tested, and the dried droplet method exhibited the best performance on MALDI-TOF-MS analysis of oligosaccharides with ISL as a matrix. For the analysis of carbohydrates, compared with popular matrices such as 2,5-dihydroxybenzoic acid (DHB) and 2,4,6-trihydroxyacetophenone (THAP), ISL exhibited outstanding matrix properties as follows: (1) higher homogeneity of crystallization thus allowing automatic data acquisition, (2) better spectral quality in terms of resolution and signal to noise ratio (SN(-1)), (3) better salt tolerance, (4) higher sensitivity, and (5) enough fragmentation yield to use LIFT-TOF/TOF MS to get richer structural information. In addition, reliable quantitative analysis of oligosaccharides with a good linearity over two concentration orders (1-100 pmol μL(-1)) and good reproducibility of the signal intensity (RSD less than 15%) were achieved using this matrix. These results give a new outlook on high-speed analysis of neutral carbohydrates by MALDI-TOF MS.
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