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Title

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

Authors
Pell, Reinhard
Clarke, Adrian
Published in Journal of Chromatography. A. 2019, vol. 1586, p. 149-153
Abstract 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.
Keywords Site-specific antibody drug conjugatesHydrophobic interaction chromatographyReversed phase liquid chromatographyMass spectrometryBiopharmaceuticals
Identifiers
PMID: 30554777
Full text
Structures
Research group Sciences analytiques
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(ISO format)
D'ATRI, Valentina et al. Is hydrophobic interaction chromatography the most suitable technique to characterize site-specific antibody-drug conjugates?. In: Journal of Chromatography. A, 2019, vol. 1586, p. 149-153. doi: 10.1016/j.chroma.2018.12.020 https://archive-ouverte.unige.ch/unige:115543

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Deposited on : 2019-04-01

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