Therapeutic monoclonal antibodies (mAbs) have grown significantly in popularity over the last 30 years as a class of human therapeutics, leading to an interesting alternative to small molecule drugs in the pharmaceutical industry. The characterization of mAbs is complex but of utmost importance, due to the occurrence of post-translational modifications (PTMs) that could hamper the drug safety and efficacy. Liquid chromatography has emerged as a key technique in the characterization of size, charge, hydrophobic, and hydrophilic protein variants. Coupled to mass spectrometry, chromatographic techniques provide well-established strategies to characterize the aforementioned structural protein variants. In this thesis, new chromatographic strategies have been developed that aim to further improve the speed and/or selectivity of these state-of-the-art characterization techniques and prepare them for the next-generation of antibody-based products such as, antibody-drug conjugates (ADCs), fusion proteins, and bi-specific antibodies.