We present a robust and general shotgun glycoproteomics approach to comprehensively profile glycoproteins in complex biological mixtures. In this approach, glycopeptides derived from glycoproteins are enriched by selective capture onto a solid support using hydrazide chemistry, followed by enzymatic release of the peptides and subsequent analysis by tandem mass spectrometry. The approach was validated using standard protein mixtures which resulted in a close to 100 % capture efficiency. Our capture approach was then applied to microsomal fractions of the cisplatin-resistant ovarian-cancer cell line IGROV-1/CP. With a protein-prophet probability value greater than 0.9, we identified a total of 302 proteins with an average protein identification rate of 136±19 (n=4) in a single LTQ nanoLC-MS experiment, and a selectivity of 91±1.6 % (n=4) for the N-linked glyco-consensus sequence. Our method has several advantages: 1) the utility of sodium-sulphite as a quencher in our capture approach to replace the SPE (solid phase extraction) step in earlier glycoprotein chemical-capture approach for removing excess sodium periodate allows the overall capture procedure to be completed in a single vessel. This improvement minimizes sample loss and increases sensitivity, and makes our protocol amenable for high throughput implementation, a feature that is essential for biomarker identification and validation of large number of clinical samples; 2) digestion of proteins initially into peptides improves solubility of large membrane proteins and exposes all of the glycosylation sites to ensure equal accessibility to capture reagents; 3) capturing glycosylated peptides can effectively reduce sample complexity and at the same time increase the confidence of MS-based protein identifications (more potential peptide identifications per protein); 4) the approach is demonstrated here on the analysis of N-linked glycopeptides, however, it can be applied equally well to O-glycoprotein analysis.