AbstractThe control of the degradation of monoclonal antibodies is one of primary steps of the biologics development process. Traditionally a range of chromatographic and electrophoretic procedures is used for this purpose. However, the most comprehensive information about the degradation process can be obtained using a multiple attribute method (MAM) approach based on bottom-up liquid chromatography–tandem mass spectrometry (LC–MS/MS). We perform a comparative evaluation of the forced degradation of omalizumab and eculizumab monoclonal antibodies obtained by the bottom-up approach, isoelectric focusing, and high-performance liquid chromatography. An advantage of HPLC–MS/MS in terms of dynamic range, specificity, and flexibility in the evaluation of degraded protein forms was demonstrated. The results show that the developed bottom-up approach can be used in the studies of the degradation of monoclonal antibodies and the routine biopharmaceutical quality control.