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Is hydrophobic interaction chromatography the most suitable technique to characterize site-specific antibody-drug conjugates?
Journal article

Is hydrophobic interaction chromatography the most suitable technique to characterize site-specific antibody-drug conjugates?

  • D'Atri V School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU - Rue Michel Servet 1, 1211, Geneva 4, Switzerland.
  • Pell R Novartis Pharma AG, Technical Research and Development, CHemical and Analytical Development (CHAD), Basel, CH4056, Switzerland.
  • Clarke A Novartis Pharma AG, Technical Research and Development, CHemical and Analytical Development (CHAD), Basel, CH4056, Switzerland.
  • Guillarme D School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU - Rue Michel Servet 1, 1211, Geneva 4, Switzerland. Electronic address: davy.guillarme@unige.ch.
  • Fekete S School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, CMU - Rue Michel Servet 1, 1211, Geneva 4, Switzerland.
  • 2018-12-18
Published in:
  • Journal of chromatography. A. - 2019
Biopharmaceuticals
Hydrophobic interaction chromatography
Mass spectrometry
Reversed phase liquid chromatography
Site-specific antibody drug conjugates
Chromatography, Liquid
Chromatography, Reverse-Phase
Cysteine
Humans
Hydrophobic and Hydrophilic Interactions
Immunoconjugates
Pharmaceutical Preparations
English Antibody drug conjugates (ADCs) belong to the fastest growing class of therapeutic agents for cancer therapy. In preclinical and clinical studies, there is a significant number of site-specific ADCs (also known as third generation ADCs), which are more homogeneous than their previous generations. These new ADC formats, in which the inter-chain disulphide bridges (hinge cysteines) are not reduced, also need to be deeply characterized. In particular, various quality attributes (QAs) have to be determined, such as free antibody level, average drug to antibody ratio (DAR) and drug distribution. In this contribution, a non-commercial site-specific conjugated ADC has been analyzed by RPLC. Our results demonstrated that RPLC has a huge potential to determine QAs and can replace the historically used HIC methods as RPLC provides better separation quality for such type of ADCs. Site-specific ADCs can be analyzed in RPLC at intact level without the need for sample preparation. A further advantage of RPLC is that it enables the direct coupling to MS and thus allows the fine identification of all eluting species.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/46712
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