AI Insight
Researchers developed RaPiD-mAb-MS, a direct infusion mass spectrometry method for peptide mapping of monoclonal antibodies that eliminates the chromatography step used in conventional LC-MS approaches. The method combines high-throughput plate-based sample preparation with direct infusion mass spectrometry, enabling analysis of 96 samples in approximately 1.5 to 2 hours, achieving greater than 95% sequence coverage across 28 unique antibodies and over 2,000 samples. RaPiD-mAb-MS reliably detects and quantifies key post-translational modifications and sequence variants, including oxidation, deamidation, isomerization, glycosylation, and sequence variants, with results comparable to conventional LC-MS methods while being up to 100 times faster.
Why it matters
This technology could substantially accelerate monoclonal antibody drug discovery and development by enabling approximately 1,000 peptide maps per day, reducing analytical bottlenecks at all development stages. The high-throughput data generation also creates opportunities for applying machine learning to predict optimal antibody variants and formulations, which could shorten timelines for bringing new biotherapeutic drugs to patients.
⚠️ Preprint – Noch nicht peer-reviewed
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Peptide mapping is a critical tool for characterizing biotherapeutic proteins and is essential for the development of monoclonal antibody drugs. Here we describe a new direct infusion technology that streamlines peptide mapping data collection and analysis, accelerating the method by up to 100-fold. This method, which we term RaPiD-mAb-MS, combines high-throughput plate-based sample preparation with direct infusion mass spectrometry analysis. RaPiD-mAb-MS allows analysis of 96 samples within ~ 1.5 to 2 hours, routinely achieves >95% sequence coverage, and has been successfully applied to 28 unique antibodies and over 2,000 samples. Here we demonstrate that RaPiD-mAb-MS detects and quantifies oxidation, deamidation, isomerization, glycosylation, and sequence variants with results comparable to conventional LC-MS based methods in a fraction of the time. Further, by eliminating chromatography, data analysis is greatly streamlined and simplified. By allowing for the collection of ~ 1,000 peptide maps per day, RaPiD-mAb-MS is positioned to accelerate all phases of antibody-based drug discovery & development and sets the stage for collection of massive datasets that would allow artificial intelligent prediction of optimal antibody variants and formulations.
Source: Rapid Peptide Mapping of Monoclonal Antibodies with Direct Infusion Mass Spectrometry