Sensitive analysis of oligosaccharides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is significantly hampered by the low ionization efficiency of oligosaccharides. Derivatization affords a feasible way to enhance the MALDI intensities of oligosaccharides by introducing an easily ionized and/or hydrophobic tag to their reducing ends. However, tagging and subsequent desalting processes are quite time-consuming. Herein, we develop a rapid and sensitive approach for oligosaccharide derivatization by using 2-hydrazinopyrimidine (2-HPM). As a result of the presence of an electron-withdrawing N-heterocycle, 2-HPM can quantitatively derivatize oligosaccharides within 15 min and selectively facilitate their ionization. Additionally, 2-HPM acts as co-matrix to enhance the MALDI signal of oligosaccharides, and therefore the tedious enrichment and purification processes prior to MALDI analysis are avoided. This approach is applied to the analysis of various oligosaccharides released from glycopeptides, glycoprotein, and biological samples. After derivatization, a significant increase of MALDI intensities (greater than 10-fold) was observed for all the tested neutral and sialylated oligosaccharides. Moreover, the enhanced fragmentation of MS/MS brings much convenience to the structural elucidation of oligosaccharides.
