Addressing Bioanalytical Needs of Antibody-Based Biotherapeutics by LC-MS

entering clinical studies [1]. The popularity is attributed to the high selectivity of these drugs which enhances their efficacy and reduces systemic toxicity, in turn, increasing the therapeutic index. In addition, antibody-based biotherapeutics have long circulatory half-lives and are less likely to undergo significant biotransformation in vivo. Since the approval of the first monoclonal antibody (mAb) drug (Orthoclone OKT3®) in the 1980s, the number of antibody-based biotherapeutics on the market and in development has reached several hundred. Recent advancements in antibody engineering and manufacturing techniques have led to generation of new biotherapeutic modalities such as multispecific mAbs, antibody-drug conjugates, ProbodyTM therapeutics and ProbodyTM drug conjugates, PEGylated antibody fragments and fragment crystallizable (Fc)-fusion proteins. The increasing complexity of the new biotherapeutic modalities pose newer bioanalytical challenges. In some instances, multiple bioanalytical assays using different analytical platforms are required to address the pharmacokinetic characterization of these new modalities.