Liquid chromatogram-mass spectrum combined analysis method and device and control system and method of liquid chromatogram-mass spectrum combined analysis device

Abstract

The invention discloses a liquid chromatogram-mass spectrum combined analysis method and device and a control system and method of the liquid chromatogram-mass spectrum combined analysis device. The analysis method comprises the following steps: carrying out one-dimensional liquid chromatography separation on a biological sample to be detected to obtain a one-dimensional eluent, carrying out two-dimensional liquid chromatography separation on the one-dimensional eluent, carrying out series on-line mass spectrometry, and directly carrying out series on-line enzymolysis and on-line trapping on the one-dimensional eluent, and carrying out series on-line two-dimensional liquid chromatography separation on the captured enzymolysis components. According to the method, on-line enzymolysis and 2D-MS are realized for a biological sample needing enzymolysis, the method has universality for the biological sample, the analysis efficiency can be effectively improved, the original analysis time of two weeks is shortened to less than two hours, the analysis cost is greatly reduced, and the method can be used for detection and analysis in industrialization and has wide application prospects. And guidance can be provided for scientifically developing antibody drug research and development.

Description

technical field [0001] The invention relates to the field of protein detection and analysis, in particular to a liquid chromatography-mass spectrometry analysis method, device, and control system and method thereof. Background technique [0002] In recent years, monoclonal antibody drugs have always occupied the core position of the global pharmaceutical market, and are also the core driving force for the rapid growth of my country's biopharmaceutical industry. The process of using animal cell culture for monoclonal antibody (mAb) production will cause the heterogeneity of quality attributes, and charge heterogeneity, as a kind of key quality attributes, may affect the structure and function of antibodies, in order to ensure the safety and security of drugs. Validity requires quality control of charge heterogeneity. [0003] At present, the most widely used antibody charge heterogeneity analysis in the industry is a product-specific salt gradient cation exchange chromatogra...

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Problems solved by technology

[0007] The technical problem to be solved by the present invention is to overcome the existing traditional mode of separation first, then collection, and then characterization. In the process of separation and analysis of monoclonal antibodies, the load is high, the throughput is low, the efficiency is poor, and the cycle time for obtaining sufficient samples long, and can only realize the defect of separation and characterization after off-line enzymatic hydrolysis, provide a liquid chromatography-mass spectrometry analysis method, device and its control system and method, using two-dimensional liquid chromatography system, through the existing technology The flexible combination of hardware such as different chromatographic columns, combined with online enzymatic digestion, first separates biological samples, especially charge variants, and then directly performs liquid chromatography-mass spectrometry (LC-MS) characterization at the peptide level, which can achieve high-throughput, Efficient charge heterogeneity characterization with reduced costs and shorter analysis cycles

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