Monoclonal antibodies are a class of biological products with the fastest growth rate in the fields of biotechnology. They are widely used in cancer, autoimmune diseases and other fields due to their advantages of targeting and obvious therapeutic effect. Host cell proteins (HCP) are a class of process impurities that cannot be removed in its production and are easy to cause immunogenicity, and HCP content determination is an important critical quality attribute in the quality control of monoclonal antibody drugs. An enzyme-linked-immunosorbent assay ( ELISA) is the most common method for HCP quantitation, but it has many limitations. As a high-precision and high-accuracy detection method, mass spectrometry has been applied to the monitoring of HCP in the production process of monoclonal antibody biological drugs, which can complement ELISA, make up for the shortcomings of ELISA method, and provide a basis for optimization of production conditions and verification of purification effect. In this paper, we summarized the application and development of mass spectrometry method in the research of monoclonal antibody HCP in recent years from three aspects: sample preparation, sample separation and data acquisition, providing reference and guidance for subsequent research on the application of mass spectrometry to HCP detection.

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