ArticleJournal of the American Society for Mass Spectrometry2017
Analysis of Monoclonal Antibodies in Human Serum as a Model for Clinical Monoclonal Gammopathy by Use of 21 Tesla FT-ICR Top-Down and Middle-Down MS/MS.
Article in Journal of the American Society for Mass Spectrometry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed.
- Top-Down and Middle-Down Mass Spectrometry of Antibodies.Molecular & cellular proteomics : MCP · 2025Review
- Improved characterization of trastuzumab deruxtecan with PTCR and internal fragments implemented in middle-down MS workflows.Analytical and bioanalytical chemistry · 2024Article
- Mass spectrometry characterization of antibodies at the intact and subunit levels: from targeted to large-scale analysis.International journal of mass spectrometry · 2023Article
- Fourier-transform ion cyclotron resonance mass spectrometry for characterizing proteoforms.Mass spectrometry reviews · 2022Review
- Next-Generation Serology by Mass Spectrometry: Readout of the SARS-CoV-2 Antibody Repertoire.Journal of proteome research · 2022Article
- Human plasma IgG1 repertoires are simple, unique, and dynamic.Cell systems · 2021Article
- Generating Informative Sequence Tags from Antigen-Binding Regions of Heavily Glycosylated IgA1 Antibodies by Native Top-Down Electron Capture Dissociation.Journal of the American Society for Mass Spectrometry · 2021Article
- Tailoring to Search Engines: Bottom-Up Proteomics with Collision Energies Optimized for Identification Confidence.Journal of proteome research · 2021Article
- Glycoproteomics Technologies in Glycobiotechnology.Advances in biochemical engineering/biotechnology · 2021Article
- Selectivity over coverage inChemical science · 2020Article
- Rapid Analysis of Reduced Antibody Drug Conjugate by Online LC-MS/MS with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.Analytical chemistry · 2020Article
- Parallel Detection of Fundamental and Sixth Harmonic Signals Using an ICR Cell with Dipole and Sixth Harmonic Detectors.Journal of the American Society for Mass Spectrometry · 2020Article
- Top-down proteomics-a near-future technique for clinical diagnosis?Annals of translational medicine · 2020Article
- Ion Activation Methods for Peptides and Proteins.Analytical chemistry · 2020Review
- Unambiguous Sequence Characterization of a Monoclonal Antibody in a Single Analysis Using a Nonspecific Immobilized Enzyme Reactor.Analytical chemistry · 2019Article
- Article
- Top-down Mass Spectrometry Analysis of Human Serum Autoantibody Antigen-Binding Fragments.Scientific reports · 2019Article
- Structural Analysis of Monoclonal Antibodies by Ultrahigh Resolution MALDI In-Source Decay FT-ICR Mass Spectrometry.Analytical chemistry · 2019Article
- Article
- Middle-down approach: a choice to sequence and characterize proteins/proteomes by mass spectrometry.RSC advances · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2-0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error ~4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background. Graphical Abstract ᅟ.
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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.