Utility of Ion Mobility Mass Spectrometry for Drug-to-Antibody Ratio Measurements in Antibody-Drug Conjugates.

J Am Soc Mass Spectrom

Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb Company, Princeton, NJ, USA.

Published: October 2015

AI Article Synopsis

  • Antibody-drug conjugates (ADCs) are becoming important in pharmaceuticals, and measuring the drug-to-antibody ratio (DAR) is crucial for determining their effectiveness and safety.
  • Traditional methods for analyzing DAR through intact protein mass spectrometry (MS) face challenges due to the variability in ADC samples, often requiring complex procedures like deglycosylation and reduction.
  • This study demonstrates the benefits of using ion mobility mass spectrometry (IM-MS) in conjunction with liquid chromatography (LC) for DAR assessments, enhancing signal quality and enabling better tracking of DAR variations across different production batches.

Article Abstract

Antibody-drug conjugates (ADCs) are emerging modalities in the pharmaceutical industry. Characterization of ADC's drug-to-antibody ratio (DAR) becomes a key assessment because of its importance in ADC efficacy and safety. DAR characterization by conventional intact protein MS analysis, however, is challenging because of high heterogeneity of ADC samples. The analysis often requires protein deglycosylation, disulfide-bond reduction, or partial fragmentation. In this study, we illustrate the practical utility of ion mobility mass spectrometry (IM-MS) in a routine LC/MS workflow for DAR measurements. This strategy allows analyte "cleanup" in the gas phase, providing significant improvement of signal-to-noise ratios of ADC intact mass spectra for accurate DAR measurements. In addition, protein drift time analysis offers a new dimension in monitoring the changes of DAR in lot-to-lot analysis.

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Source
http://dx.doi.org/10.1007/s13361-015-1203-1DOI Listing

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