title: Utility of Ion Mobility Mass Spectrometry for Drug-to-Antibody Ratio Measurements in Antibody-Drug Conjugates.
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.
authors.affiliation: Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb Company, Princeton, NJ, USA. richard.huang2@bms.com.
authors.forename: Richard Y-C
authors.initials: RY
authors.lastname: Huang
authors.affiliation: Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb Company, Princeton, NJ, USA.
authors.forename: Ekaterina G
authors.initials: EG
authors.lastname: Deyanova
authors.affiliation: Biologics Discovery California, Research and Development, Bristol-Myers Squibb Company, Redwood City, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Passmore
authors.affiliation: Biologics Discovery California, Research and Development, Bristol-Myers Squibb Company, Redwood City, CA, USA.
authors.forename: Vangipuram
authors.initials: V
authors.lastname: Rangan
authors.affiliation: Biologics Discovery California, Research and Development, Bristol-Myers Squibb Company, Redwood City, CA, USA.
authors.forename: Shrikant
authors.initials: S
authors.lastname: Deshpande
authors.affiliation: Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb Company, Princeton, NJ, USA.
authors.forename: Adrienne A
authors.initials: AA
authors.lastname: Tymiak
authors.affiliation: Bioanalytical and Discovery Analytical Sciences, Research and Development, Bristol-Myers Squibb Company, Princeton, NJ, USA. guodong.chen@bms.com.
authors.forename: Guodong
authors.initials: G
authors.lastname: Chen
mesh_terms: D002851:Chromatography, High Pressure Liquid; D018796:Immunoconjugates / Q000032:analysis* / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry
chemical_list: D018796:Immunoconjugates; D004364:Pharmaceutical Preparations
keywords: ADC; DAR; Ion mobility; MS