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

Bioanalysis. 2014;6(13):1747-58. doi: 10.4155/bio.14.64. Epub 2014 Mar 24.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Antibodies, Monoclonal / blood*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism
  • Calibration
  • Chromatography, High Pressure Liquid* / standards
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / metabolism
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Heavy Chains / metabolism
  • Molecular Sequence Data
  • Peptides / analysis
  • Peptides / chemistry
  • Protein Structure, Tertiary
  • Tandem Mass Spectrometry* / standards
  • Trypsin / metabolism

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Peptides
  • Trypsin