ArticleAnalytical chemistry2020
Rapid and Simultaneous Characterization of Drug Conjugation in Heavy and Light Chains of a Monoclonal Antibody Revealed by High-Resolution Ion Mobility Separations in SLIM.
Article in Analytical chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Resolving Isomeric Structures in Natural Complex Carbohydrates: A Comparative Study of SLIM and Cyclic Ion Mobility Platforms.Rapid communications in mass spectrometry : RCM · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- High Resolution Ion Mobility Enables the Separation of α-Galactose Containing Glycans from Their Non-α-Galactose Isomers.Journal of biomolecular techniques : JBT · 2026Article
- New Frontiers in ADC Analysis: Advances in Chromatography, Electrophoresis, and Mass Spectrometry.The AAPS journal · 2025Review
- Performance Evaluation of Constant Field and Traveling Wave-Based Structures for Lossless Ion Manipulations Devices Coupled to Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2025Article
- Ultrafast Microdroplet Digestion of Antibodies with Fc-Silencing Mutations.Analytical chemistry · 2025Article
- Navigating the future of gastric cancer treatment: a review on the impact of antibody-drug conjugates.Cell death discovery · 2025Review
- Cyclable Variable Path Length Multilevel Structures for Lossless Ion Manipulations (SLIM) Platform for Enhanced Ion Mobility Separations.Analytical chemistry · 2024Article
- Enhancing the Depth of Analyses with Next-Generation Ion Mobility Experiments.Annual review of analytical chemistry (Palo Alto, Calif.) · 2023Review
- Development of a Structure for Lossless Ion Manipulations (SLIM) High Charge Capacity Array of Traps.Analytical chemistry · 2023Article
- Rapid Characterization of Antibodies via Automated Flow Injection Coupled with Online Microdroplet Reactions and Native-pH Mass Spectrometry.Analytical chemistry · 2023Article
- Separation and Collision Cross Section Measurements of Protein Complexes Afforded by a Modular Drift Tube Coupled to an Orbitrap Mass Spectrometer.Analytical chemistry · 2022Article
- Accelerating prototyping experiments for traveling wave structures for lossless ion manipulations.Talanta · 2022Article
- Enhanced Top-Down Protein Characterization with Electron Capture Dissociation and Cyclic Ion Mobility Spectrometry.Analytical chemistry · 2022Article
- High-Throughput Multi-attribute Analysis of Antibody-Drug Conjugates Enabled by Trapped Ion Mobility Spectrometry and Top-Down Mass Spectrometry.Analytical chemistry · 2021Article
- Microdroplet Ultrafast Reactions Speed Antibody Characterization.Analytical chemistry · 2021Article
- Recent advances in high-resolution traveling wave-based ion mobility separations coupled to mass spectrometry.Mass spectrometry reviewsReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Antibody-drug conjugates (ADCs) have recently gained traction in the biomedical community due to their promise for human therapeutics and an alternative to chemotherapy for cancer. Crucial metrics for ADC efficacy, safety, and selectivity are their drug-antibody ratios (DARs). However, DAR characterization (i.e., determining the average number of conjugated drugs on the antibody) through analytical methods remains challenging due to the heterogeneity of drug conjugation as well as the numerous post-translational modifications possible in the monoclonal antibody. Herein, we report on the use of high-resolution ion mobility spectrometry separations in structures for lossless ion manipulations coupled to mass spectrometry (SLIM IMS-MS) for the rapid and simultaneous characterization of the drug load profile (i.e., stoichiometric distribution of the number of conjugated drugs present on the mAb), determination of the weighted average DAR in both the heavy and light chains of a model antibody-drug conjugate, and calculation of the overall DAR of the ADC. After chemical reduction of the ADC and a subsequent 31.5 m SLIM IMS separation, the various drug-bound antibody species could be well resolved for both chains. We also show significantly higher resolution separations were possible for these large ions with SLIM IMS as compared to ones performed on a commercially available (1 m) drift tube IMS-MS platform. We expect high-resolution SLIM IMS separations will augment the existing toolbox for ADC characterization, particularly to enable the rapid optimization of DAR for a given ADC and thus better understand its potential toxicity and potency.
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Registered trials
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