Bioanalytical Assays for Pharmacokinetic and Biodistribution Study of Antibody-Drug Conjugates.

ABSTRACT

Antibody-drug conjugates (ADCs) are produced by the chemical linkage of cytotoxic agents and monoclonal antibodies. The complexity and heterogeneity of ADCs and the low concentration of cytotoxic agent released in vivo poses big challenges to their bioanalysis. Understanding the pharmacokinetic behavior, exposure-safety, and exposure-efficacy relationships of ADCs is needed for their successful development. Accurate analytical methods are required to evaluate intact ADCs, total antibody, released small molecule cytotoxins, and related metabolites. The selection of appropriate bioanalysis methods for comprehensive analysis of ADCs is mainly dependent on the properties of cytotoxic agents, the chemical linker, and the attachment sites. The quality of the information about the whole pharmacokinetic profile of ADCs has been improved due to the development and improvement of analytical strategies for detection of ADCs, such as ligand-binding assays and mass spectrometry-related techniques. In this article, we will focus on the bioanalytical assays that have been used in the pharmacokinetic study of ADCs and discuss their advantages, current limitations, and potential challenges. SIGNIFICANCE STATEMENT This article describes bioanalysis methods which have been used in pharmacokinetic study of ADCs and discusses the advantages, disadvantages and potential challenges of these assays. This review is useful and helpful and will provide insights and reference for bioanalysis and development of ADCs.