ArticlemAbs2019
Comprehensive characterisation of the heterogeneity of adalimumab via charge variant analysis hyphenated on-line to native high resolution Orbitrap mass spectrometry.
Article in mAbs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 92 citations in OpenAlex.
- Article
- Native CZE-MS analysis of antibodies and hemoglobin using protein-adapted CZE and ESI conditions for detailed proteoform characterization.Analytical and bioanalytical chemistry · 2026Article
- Accelerating microfluidic capillary electrophoresis-mass spectrometry for charge-variant and glycoform analysis of intact monoclonal antibodies.Analytical and bioanalytical chemistry · 2026Article
- Article
- Developments in Ion Exchange Chromatography-Mass Spectrometry for the Characterization of Intact Proteins and Proteoforms.Journal of separation science · 2025Review
- Charge variant analysis of monoclonal antibodies by CZE-MS using a successive multiple ionic-polymer layer coating based on diethylaminoethyl-dextran.Electrophoresis · 2025Article
- Detection of host cell microprotein impurities in antibody drug products.Nature communications · 2024Article
- Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics.Journal of pharmaceutical analysis · 2024Review
- Mobile Affinity Selection Chromatography Analysis of Therapeutic Monoclonal Antibodies.Analytical chemistry · 2023Article
- Consistency of Product Quality for SB5, an Adalimumab Biosimilar.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Article
- Rapid multi-attribute characterization of intact bispecific antibodies by a microfluidic chip-based integrated icIEF-MS technology.Electrophoresis · 2023Article
- Method Development and Qualification of pH-Based CEX UPLC Method for Monoclonal Antibodies.Biotech (Basel (Switzerland)) · 2022Article
- Approaches to Heterogeneity in Native Mass Spectrometry.Chemical reviews · 2022Review
- Studying protein structure and function by native separation-mass spectrometry.Nature reviews. Chemistry · 2022Review
- Global characterization of modifications to the charge isomers of IgG antibody.Journal of pharmaceutical analysis · 2022Article
- Detection and quantitation of host cell proteins in monoclonal antibody drug products using automated sample preparation and data-independent acquisition LC-MS/MS.Journal of pharmaceutical analysis · 2021Article
- A Native Mass Spectrometry-Based Assay for Rapid Assessment of the Empty:Full Capsid Ratio in Adeno-Associated Virus Gene Therapy Products.Analytical chemistry · 2021Article
- Simultaneous Monitoring of Monoclonal Antibody Variants by Strong Cation-Exchange Chromatography Hyphenated to Mass Spectrometry to Assess Quality Attributes of Rituximab-Based Biotherapeutics.International journal of molecular sciences · 2021Article
- Characterization of Protein Glycoforms at Intact Level by Orbitrap Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Comparison of Three Complementary Analytical Techniques for the Evaluation of the Biosimilar Comparability of a Monoclonal Antibody and an Fc-Fusion Protein.Frontiers in chemistry · 2021Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Charge variant analysis is a widely used tool to monitor changes in product quality during the manufacturing process of monoclonal antibodies (mAbs). Although it is a powerful technique for revealing mAb heterogeneity, an unexpected outcome, for example the appearance of previously undetected isoforms, requires further, time-consuming analysis. The process of identifying these unknowns can also result in unwanted changes to the molecule that are not attributable to the manufacturing process. To overcome this, we recently reported a method combining highly selective cation exchange chromatography-based charge variant analysis with on-line mass spectrometric (MS) detection. We further explored and adapted the chromatographic buffer system to expand the application range. Moreover, we observed no salt adducts on the native protein, also supported by the optimal choice of MS parameters, resulting in increased data quality and mass accuracy. Here, we demonstrate the utility of this improved method by performing an in-depth analysis of adalimumab before and after forced degradation. By combining molecular mass and retention time information, we were able to identify multiple modifications on adalimumab, including lysine truncation, glycation, deamidation, succinimide formation, isomerisation, N-terminal aspartic acid loss or C-terminal proline amidation and fragmentation along with the N-glycan distribution of each of these identified proteoforms. Host cell protein (HCP) analysis was performed using liquid chromatography-mass spectrometry that verified the presence of the protease Cathepsin L. Based on the presence of trace HCPs with catalytic activity, it can be questioned if fragmentation is solely driven by spontaneous hydrolysis or possibly also by enzymatic degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.