Antibody-based biotherapeutics are the fastest growing category of therapeutics 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 mar- ket 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, Probody™ therapeutics and Probody™ drug conjugates, PEGylated antibody frag- ments 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 re- quired to address the pharmacokinetic characterization of these new modalities. Bioanalysis by LC-MS for Antibody-Based Biotherapeutics Traditionally, ligand binding assays (LBA), primarily enzyme-linked immunosorbent assay (ELISA), have been the gold standard for protein quantification. ELISA has numerous benefits such as high-sensitivity, high-throughput, low-cost and ease of use. LBAs require high-quality critical reagents, that have high selectivity for the biotherapeutic drug, for capture and detection. The availability of a highly selective critical reagents is a major challenge of LBAs. The time of production of a high-qual- ity critical reagent can prolong the method development time. The narrow dynamic range (typically around 100-fold) and high susceptibility to matrix interferences are other limitations of the LBAs. Over past decade, liquid chromatography and mass spectrometry (LC-MS) has emerged as an alternate tool for quantification of proteins [2]. Rapid method de- velopment, broader dynamic range, higher selectivity and multiplexing capabilities are the main advantages of the LC-MS platform in comparison to the LBAs. The advancements in the mass spectrometric instrumentation and sample preparation methodology has enabled the use LC-MS as a complementary bioanalytical tool and in some applications as a mainstream bioanalytical tool for protein biothera- peutics. Quantitative bioanalysis of antibody-based biotherapeutics by LC-MS is typically PPD Laboratories, Richmond, VA 23230, USA. Correspondence: PPD Laboratories, 2244 Dabney Road, Richmond, VA 23230, USA. Phone: +1 804 977 8491; Email: morse.faria@ppdi.com Addressing Bioanalytical Needs of Antibody-Based Biotherapeutics by LC-MS Morse Faria FOREWORD Citation: Faria M. Addressing Bioanalytical Needs of Antibody-Based Biothera- peutics by LC-MS. J Appl Bioanal 6(1), 7-11 (2020). Open Access & Copyright: ©2020 Faria M. This is an open access article distributed under the terms of the Creative Commons Attri- bution License (CC-BY) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Funding & Manuscript writing assistance: The author has declared that no fund- ing nor writing assistance was utilized in the production of this article. Financial & Competing interests: The author is employee of PPD Labo- ratories USA. The author has declared that no competing interest exist. Journal of Applied Bioanalysis JOURNAL OF APPLIED BIOANALYSIS Volume 6, No. 1 | January 2020 7 http://dx.doi.org/10.17145/jab.20.003 openaccess