, Volume 28, Issue 4, pp 383–391 | Cite as

Practical Considerations for the Pharmacokinetic and Immunogenic Assessment of Antibody–Drug Conjugates

  • Melody Sauerborn
  • William van Dongen
Review Article


Currently, the most bioanalytically challenging drugs are antibody–drug conjugates (ADCs), constructs comprising a monoclonal antibody and a cytotoxic drug connected by a linker. The bioanalytical challenges arise from the heterogeneous nature of ADCs and their complex in vivo behavior, resulting in a high number of analytes to be measured. Measuring the concentration of biologics in blood/plasma/serum is a necessity to properly assess their pharmacokinetic (PK)/pharmacodynamic behaviors in vivo. An additional bioanalytical challenge is to monitor the stability of the ADCs, as cytotoxic drugs released from the ADC in blood circulation may pose a potential safety risk because of their high cytotoxic potency. The nature of ADCs does not only complicate bioanalysis, but also immunogenicity assessment. Questions, such as ‘Which part of the ADCs is the anti-drug antibodies directed against?’ may arise, and their answer normally includes several immunogenicity risk assessment strategies. This review will focus on the bioanalytical challenges of ADCs, current approaches involving ligand-binding assays (LBAs), liquid chromatography and mass spectrometry platforms, and recommendations on which approach to use for which stage of drug development, and will close with immunogenicity assessment. In order to appropriately tackle the bioanalytical and immunogenic challenges of ADCs and consider every angle, the authors of this review have expertise in ligand binding and liquid chromatography–mass spectrometry.


Cetuximab Cytotoxic Drug Therapeutic Antibody Complementarity Determine Region Brentuximab Vedotin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Acknowledgments and Disclosures

The authors declare no conflicts of interest in this work and that everything was written by the stated authors.


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of BioanalysisTNO TriskelionZeistThe Netherlands

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