PK assays for antibody-drug conjugates: case study with ado-trastuzumab emtansine

Bioanalysis. 2013 May;5(9):1025-40. doi: 10.4155/bio.13.72.

Abstract

Background: Antibody-drug conjugates (ADCs) combine the characteristics of large-molecule biologics and small-molecule drugs and are heterogeneous mixtures that can biotransform in vivo, resulting in additional complexity. ADC bioanalytical strategies require novel analytical methods, as well as existing large- and small-molecule methods. Because ADCs in late-stage clinical development are relatively new, regulatory guidelines and standard industry best practices for developing strategies for bioanalytical PK assays are still being established.

Results: A PK assay strategy was developed that included comprehensive novel reagent and assay characterization approaches for the ADC ado-trastuzumab emtansine (T-DM1).

Conclusion: The bioanalytical strategy was successfully applied to the drug development of T-DM1 and ensured that key analytes were accurately measured in support of nonclinical and clinical development.

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Antibodies, Monoclonal / analysis*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / analysis*
  • Antibodies, Monoclonal, Humanized / metabolism
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Chromatography, Liquid
  • Drug Design
  • Enzyme-Linked Immunosorbent Assay*
  • Immunoconjugates / analysis*
  • Immunoconjugates / pharmacokinetics
  • Mass Spectrometry
  • Maytansine / analogs & derivatives*
  • Maytansine / analysis
  • Maytansine / metabolism
  • Maytansine / pharmacokinetics
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoconjugates
  • Maytansine
  • Trastuzumab
  • Ado-Trastuzumab Emtansine