title: Antibody-drug conjugate characterization by chromatographic and electrophoretic techniques.
abstract: Due to the inherent structure complexity and component heterogeneity of antibody drug conjugates (ADCs), separation technologies play a critical role in their characterization. In this review, we focus on chromatographic and electrophoretic approaches used to characterize ADCs with respect to drug-to-antibody ratio, drug distribution and conjugation sites, free small molecule drugs, charge variants, aggregates and fragments, etc. Chromatographic techniques including reversed-phase, ion exchange, size exclusion, hydrophobic interaction, two-dimensional liquid chromatography, and gas chromatography as well as capillary electrophoretic techniques including capillary electrophoresis sodium dodecyl sulfate, capillary zone electrophoresis and capillary isoelectric focusing are reviewed for their applications in the characterization of ADCs.
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.affiliation: Protein Analytical Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Protein Analytical Chemistry, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Stella
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Medley
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Gruenhagen
authors.affiliation: Small Molecule Pharmaceutical Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: zhang.kelly@gene.com.
authors.forename: Kelly
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002845:Chromatography / Q000295:instrumentation / Q000379:methods*; D004586:Electrophoresis / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*
chemical_list: D018796:Immunoconjugates; D004364:Pharmaceutical Preparations
keywords: Aggregations; Antibody drug conjugate (ADC); Charge variants; Critical quality attribute (CQA); Drug distribution; Drug-to-antibody ratio (DAR); Free drug analysis; Peptide mapping