Due to a lack of specific chromatographic signals, targeted separation of saccharide was usually hard to perform. MS was able sensitively to identify different oligosaccharides according to their diverse molecular mass. Meanwhile, SEC was able to separate samples based on the difference in their molecular masses. Moreover, SEC could easily be scaled up, and the distribution coefficient of each particular sample was almost constant using the same SEC resin. A combination of SEC and MS would provide a feasible protocol for the targeted separation of oligosaccharides.