Native Mass Spectrometry Coupled With HIC for Antibody Impurity Analysis
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Solution Overview
Problem
Current methods for characterizing therapeutic peptides and proteins are inadequate for rapid and sensitive high-throughput analysis, particularly in monitoring post-translational modifications and impurities during production and purification, which affects the safety, efficacy, and shelf life of biopharmaceutical products.
Innovation Solution
The implementation of hydrophobic interaction chromatography-coupled native mass spectrometry provides a rapid and sensitive high-throughput method for characterizing peptides and proteins, enabling the identification and quantification of post-translational modifications, impurities, and drug-to-antibody ratios, using a chromatography column with hydrophobic groups and a mass spectrometer under native conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional characterization methods are used for therapeutic peptides and proteins, then the analysis can be conducted with standard equipment, but the analysis speed and sensitivity are insufficient for rapid high-throughput monitoring
Solution Approach 1:
The patent combines hydrophobic interaction chromatography (HIC) with native mass spectrometry (MS) into an online coupled system. The HIC separation module is directly connected to the native MS detection module, allowing simultaneous achievement of high-throughput separation and sensitive detection. This integration enables rapid analysis while maintaining high detection sensitivity for post-translational modifications and impurities.
Solution Approach 2:
The patent introduces a hydrophobic interaction chromatography column as an intermediary component between the sample injection and mass spectrometer. The HIC column separates complex biopharmaceutical samples based on hydrophobicity, providing purified fractions to the mass spectrometer for sensitive detection. This intermediary separation step enhances both analysis speed and detection sensitivity.
2Productivity
If conventional chromatography methods are used for separating and characterizing biopharmaceutical products, then the equipment is readily available, but the method cannot provide rapid and sensitive high-throughput analysis
Solution Approach 1:
The patent implements continuous online coupling between HIC separation and native MS detection. The system operates continuously with the mass spectrometer constantly analyzing eluate from the HIC column without interruption or manual intervention. This continuous operation enables high-throughput analysis while minimizing analysis time for each sample.
Solution Approach 2:
The patent performs preliminary separation of the biopharmaceutical sample using hydrophobic interaction chromatography before mass spectrometry detection. The HIC column pre-separates complex mixtures into distinct components based on hydrophobicity, reducing sample complexity before analysis and enabling faster, more efficient detection by the mass spectrometer.
3Reliability
If extensive characterization is performed to ensure product quality, then safety and efficacy are verified, but the process becomes time-consuming and reduces manufacturing efficiency
Solution Approach 1:
The patent replaces conventional mechanical detection methods with mass spectrometry-based detection. Native MS provides sensitive and specific detection of post-translational modifications, impurities, and product variants with high precision. This substitution maintains rigorous product quality assurance while significantly reducing analysis time and improving manufacturing efficiency.
Solution Approach 2:
The patent utilizes native mass spectrometry conditions that preserve the native state of biopharmaceutical proteins, analyzing them under physiological pH and ionic strength conditions. This parameter optimization enables comprehensive characterization of product quality attributes including glycosylation, oxidation, and aggregation states in a single rapid analysis, ensuring reliability while improving productivity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for precise and accurate characterization of biopharmaceutical products, improving manufacturing processes by providing rapid insights into the quality attributes of therapeutic peptides and proteins, ensuring their safety and efficacy.
Implementation Method 1
contacting the sample to a solid surface, wherein the solid surface comprises a hydrophobic group
Implementation Method 2
characterizing the at least one peptide or protein in the at least one eluent under native conditions using a mass spectrometer
Data Source
AI summary
The present invention provides rapid, sensitive high-throughput methods and systems for characterizing peptides or proteins using hydrophobic interaction chromatography-coupled native mass spectrometry to improve manufacturing process of biopharmaceutical products, such as identifying impurities during antibody purification, monitoring post-translational modification variants during production, or characterizing drug-to-antibody ratio of antibody-drug conjugates. The separation profiles of the peptides or proteins are generated and compared to identify or qualify the peptides or proteins.