Native and methyl-esterified sialylated glycans were analyzed with 2,4,6-trihydroxyacetophenone(THAP)and 2,5-dihydroxybenzoic acid(DHB)as matrix by a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer(MALDI-TOF MS).High quality negative-ion spectra of commercial sialylated glycan were obtained with THAP as matrix.Detection limit of the glycan was less than 0.1 pmol.After methyl esterification of sialic acid(SA)residue,sialylated glycans were detected sensitively in the positive-ion mode using DHB as matrix.Neutral and sialylated glycans from the mixture of asialofetuin and fetuin were methylesterified and simultaneously recognized in one manipulation.Methyl esterification of SA residue offers a convenient and sensitive way to identify the structure of N-linked glycans for glycan profiling. Native and methyl-esterified sialylated glycans were analyzed with 2,4,6-trihydroxyacetophenone (THAP) and 2,5-dihydroxybenzoic acid (DHB) as matrix by a matrix-assisted laser desorption / ionization time-of-flight mass spectrometer -TOF MS). High quality negative-ion spectra of commercial sialylated glycan were obtained with THAP as matrix. Detection limit of the glycan was less than 0.1 pmol. After methyl esterification of sialic acid (SA) residue, sialylated glycans were detected sensitively in the positive-ion mode using DHB as matrix. Neutral and sialylated glycans from the mixture of asialofetuin and fetuin were methylesterified and simultaneously recognized in one manipulation. Methyl esterification of SA residue offers a convenient and sensitive way to identify the structure of N-linked glycans for glycan profiling.