Charged aerosol detection enables sensitive, direct measurement of glycans with no need to perform labeling reactions. Detection limits for native glycans are in the low pmol (ng on-column) range. The UHPLC-CAD method developed to measure native glycans is precise, with retention time precision better than 0.1% RSD and peak area precision averaging 2.8 % RSD for the major sialylated N-glycans of bovine fetuin. UHPLC-CAD allows accurate quantification of glycans with appropriate standards, and by responding similarly to all non-volatile analytes, yields simple, accurate and precise estimates of relative concentration even in the absence of pure primary standards.