Abstract
Remarkable methodological advances in the past decade have expanded the application of liquid chromatography coupled with mass spectrometry (LC/MS) analysis of biotherapeutics. Currently, LC/MS represents a promising alternative or supplement to the traditional ligand binding assay (LBA) in the pharmacokinetic, pharmacodynamic, and toxicokinetic studies of protein drugs, owing to the rapid and cost-effective method development, high specificity and reproducibility, low sample consumption, the capacity of analyzing multiple targets in one analysis, and the fact that a validated method can be readily adapted across various matrices and species. While promising, technical challenges associated with sensitivity, sample preparation, method development, and quantitative accuracy need to be addressed to enable full utilization of LC/MS. This article introduces the rationale and technical challenges of LC/MS techniques in biotherapeutics analysis and summarizes recently developed strategies to alleviate these challenges. Applications of LC/MS techniques on quantification and characterization of antibody biotherapeutics are also discussed. We speculate that despite the highly attractive features of LC/MS, it will not fully replace traditional assays such as LBA in the foreseeable future; instead, the forthcoming trend is likely the conjunction of biochemical techniques with versatile LC/MS approaches to achieve accurate, sensitive, and unbiased characterization of biotherapeutics in highly complex pharmaceutical/biologic matrices. Such combinations will constitute powerful tools to tackle the challenges posed by the rapidly growing needs for biotherapeutics development.
Footnotes
- Received May 3, 2014.
- Accepted August 28, 2014.
This work was supported, in part, by National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grants U54 HD071594, HD075363], National Institute on Drug Abuse [Grant DA027528], National Institute of Allergy and Infectious Diseases [Grant AI060260], and National Heart, Lung, and Blood Institute [Grant HL103411], by the Center for Protein Therapeutics, and by American Heart Association (AHA) award [12SDG9450036] (all to J.Q.).
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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