Characterization of biologics, especially mAbs is a challenge task in order to ensure safety, efficacy and potency of a therapeutic agent due to the heterogeneity of the structure happened throughout the steps of cell culture process, purification process and storage. The presence of positively charged and negatively charged amino acids and negatively charged glycans (sialic acids) means that mAbs exist as multiple charged species. Understanding which amino acids or glycans are involved and their specific location within mAb is of paramount importance. Traditional ion exchange chromatography can enable the separation of some charge variants, particularly those positioned on the surface of the protein. However, microfluidic capillary electrophoresis-mass spectrometry (microfluidic CE-MS) to analyze intact mAb and to assess the root cause of the stressed mAb provides a very powerful direct and generic tool for separation and identification of charge heterogeneity of mAbs.