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Combination Strategy of Reactive and Catalytic Matrices for Qualitative and Quantitative Profiling of N-Glycans in MALDI-MS

Zhao, Xiaoyong, Guo, Cheng, Huang, Yu, Huang, Lili, Ma, Ge, Liu, Yaqin, He, Quan, Wang, Huiwen, Chen, Kunsong, Pan, Yuanjiang
Analytical chemistry 2019 v.91 no.14 pp. 9251-9258
biomarkers, blood serum, carbohydrates, catalytic activity, colorectal neoplasms, derivatization, desorption, ionization, matrix-assisted laser desorption-ionization mass spectrometry, patients, quantitative analysis
Qualitative and quantitative analysis of N-glycans by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is hampered mainly by the low ionization efficiency of analytes and their poor cocrystallization with traditional organic acid matrices. In the present study, a combination strategy of reactive and catalytic matrices (CSRCM) was proposed for the on-target derivatization and detection of reducing N-glycans: a novel reactive matrix, i.e., 2,5-dihydroxybenzohydrazide (DHBH), having a skeleton structure similar to that of DHB, was designed and synthesized, and this reactive matrix was mixed with catalytic matrix DHB to form a rationally combinatorial matrix (DHB/DHBH). Qualitatively, DHB/DHBH could improve the ionization efficiency of reducing carbohydrates significantly. Quantitatively, the acid–base chemistry of DHB/DHBH leads to a uniform cocrystallization of analytes-matrix mixtures. Consequently, CSRCM provides accurate quantitation for N-glycans with high derivatization efficiency and good linearity (R² > 0.99) within 2 orders of magnitude on the basis of an internal standard method. Furthermore, the CSRCM was successfully applied to evaluating N-glycan in serum samples of colorectal cancer patients, thus showing potential in clinical applications for biomarker discovery.