Generic method approaches for monoclonal antibody therapeutics analysis using both ligand binding and LC-MS/MS techniques.

Abstract

Monoclonal antibody (mAb) and mAb-derived biotherapeutics are being developed to interact with specific target molecule(s) to intervene disease formation or progression. LC-MS/MS methods have emerged to compensate for the limitations of conventional ligand-binding assays. Application of a generic LC-MS/MS method to multiple mAb candidates can save method development time as most mAb biotherapeutics are IgG 1, 2 and 4 isotypes. Three common components are essential to a generic LC-MS/MS method: a common workflow, a common surrogate peptide and the corresponding stable isotope-labeled internal standard. The generic LC-MS/MS method is translatable from a single- into a multiple-analyte method, and from a generic into a specific method. Strategies and caveats on method applications are discussed in this chapter.