An exploratory universal LC-MS/MS assay for bioanalysis of hinge region-stabilized human IgG4 mAbs in clinical studies.

Background: Due to the increasing number of monoclonal antibody (mAb) drug candidates entering clinical development, bioanalytical laboratories can benefit from generic liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays capable of quantifying a variety of human mAb-based therapeutic drug candidates in plasma/serum samples from clinical studies. Results: We have developed and evaluated an exploratory LC-MS/MS assay capable of quantifying hinge region-stabilized IgG4 therapeutic mAb drugs and drug candidates in clinical samples. The exploratory assay is based upon a single universal IgG4' surrogate peptide. Conclusion: The novel exploratory LC-MS/MS assay reported herein, upon further refinement and full validation, is predicted to enable bioanalytical scientists to quantify all hinge region-stabilized human IgG4 therapeutic mAbs in human studies without having to develop a new assay for every new stabilized IgG4 mAb entering clinical development.