The maintenance of higher order structure (HOS) in proteins is vital to performance,activity, and function in biological systems. Monoclonal antibodies (mAbs) are biotherapeutic monoclonal antibodies that are used to fight diseases such as cancer and rheumatoid arthritis. mAbs comprise a large piece of the pharmaceutical drug market, with projected sales expected to reach $130-220 billion USD by the year 2022. Deleterious modifications that occur on the primary level of these protein substrates alter their tertiary and quaternary structure influencing activity. The development of laboratory methods for the quantitation of post-translational modifications are essential to the monitoring and quantitation of post-translational modifications in pharmaceutical products. HPLC-MS has proven effective in the rapid analysis of proteins and their modifications. The measurable difference in mass along with physical separation of these substrates with Liquid Chromatography (LC) allows mass spectrometry-based analysis methods to be used. INDEX WORDS: Liquid Chromatography, Mass Spectrometry, Higher Order Structure, Monoclonal Antibodies, Post-Translational Modifications, Liquid Chromatography