API quality is the key and source of drug quality control. Among them, the research and control of impurities is related to the clinical safety of drugs, and therefore becomes one of the key links in API quality control. In addition to the pharmacological activity of the drug itself, the adverse reactions in the clinical use of drugs are sometimes closely related to the impurities in the drugs and must be strictly controlled. Accurately distinguish and determine the content of impurities by selecting appropriate analysis methods, and determine the reasonable limits of impurities through the results of comprehensive pharmacy, toxicology and clinical studies. Through the source control of the starting raw materials, the process control of the preparation process, the packaging materials, the storage conditions and the terminal control measures such as the establishment of the validity period, and the control of impurities within a safe and reasonable range is the ultimate goal of impurity research.
Impurities refer to substances that are produced or introduced in the process of drug production, transportation, storage, etc. that affect the purity of the drug. Pharmaceutical impurities are divided into three categories: inorganic impurities, organic impurities and residual solvents. Among them, inorganic impurities mainly refer to catalysts, inorganic salts, ligands, reagents, etc. added in the preparation of API; organic impurities mainly refer to process impurities such as intermediates and by-products, as well as organic substances produced by drug degradation, association or reaction between drugs; residual solvents mainly refer to the residues of organic solvents in production.
The basic idea of impurity research and control is to start with the analysis of impurity sources, combined with the actual production process and structural characteristics of the product to analyze various potential impurities such as intermediates, by-products, degradation products, and reaction materials that may exist in the product. Through the impurity spectrum analysis, we have a comprehensive understanding of the impurity profile of the product. According to the risk level of various potential impurities, appropriate analysis methods are established in a targeted manner to ensure the effective detection and confirmation of various potential impurities.
In the research of API, the detection and control of impurities are very important. Whether the impurities of API can be fully and accurately controlled is directly related to the clinical safety, quality controllability and product stability of the drug. Therefore, impurity research is one of the key elements of API quality assurance, and it is also an area where domestic and foreign drug research and development are focused, deepened, and rapidly developed. With the continuous in-depth research on API impurities, the detection and control of genotoxic impurities, metal impurities, and antibiotic impurities have become the focus of the research and control of API impurities in recent years, and important progress has been made.
Whether the impurities in drugs can be fully and accurately controlled is directly related to the quality control and safety of the drugs. The research and control of impurities in API is the prerequisite and key link to ensure the safety and quality control of drugs. It is an important indicator of drug consistency evaluation.