Glycosylation is one of the most common and important post-translational modifications. Quantitative analysis of intact N-glycopeptides is critical to understand the role of protein glycosylation in physiological and pathological processes. In this work, we developed a novel approach called methylamine stable isotope labeling (MeSIL) to relatively quantify intact N-glycopeptides through one step isotopic labeling. Isotopic methylamine was employed to label both the sialic acid residues of glycans and the carboxyl groups on the peptide moiety, and followed by the mixing of samples for mass spectrometric analysis. The relative abundance of intact N-glycopeptides between two samples was obtained by comparing the signal of the particular peak pairs with a 3*N Da mass shift (where N is an integer correlating with the number of carboxylic acids within the glycopeptides). Additionally, the number of sialylated glycopeptides can be distinguished simultaneously through the mass difference after labeling. The MeSIL str