| Piperaquine phosphate is a critical anti-malarial chemical drug,and it is used primarily in Africa and Southeast Asia and in national strategic stockpiles.In order to improve the quality,safety and effectiveness of drugs,this thesis describes the quality study on API piperaquine phosphate in accordance with the requirements of the international mainstream market.Combined with ICH requirements,the genetoxic impurity 1-bromo-3-chloropropane was controlled within 1.2ppm according to the dosage and the treatment cycle.In this paper,the structure identification,related substances and genotoxic impurity analysis methods,and stability of piperaquine phosphate were studied.Specific research conclusions are as follows:1.Establishment of quality standards: Establishment of key quality attributes such as related substances and genotoxic impurities.2.Structure confirmation: Piperaquine phosphate was confirmed by physical and chemical properties,elemental analysis,infrared spectrophotometry,uv spectrophotometry,nuclear magnetic resonance hydrogen spectrum,nuclear magnetic resonance carbon spectrum,mass spectrometry,DSC analysis,powder X-ray diffraction,etc.3.Establishment and verification of analysis methods: According to established quality standards,find and verify analysis methods.4.Stability study: Accelerated and long-term stability studies were carried out to improve the stability test temperature to adapt to the environmental temperature of the drug used area.At the same time,the related substances and genotoxic impurity of quality standards were studied.To sum up,the quality standard of piperaquine phosphate was determined in this paper,and the related substance limit was tightened to control the genotoxic impurities and other factors.Control the genotoxic impurity and so on,improve the product quality and meet the latest requirements of the international mainstream market.The analysis method established in this paper is scientific and effective,and the analysis method can analyze the key quality attributes and guarantee the quality of drugs.The structure verifies that the substance of the synthetic API is correct.Stability studies ensure that piperaquine phosphate is of controllable quality,safe and effective throughout its life cycle.The above work can effectively reduce the side effects of clinical medication and provide a safety guarantee for clinical medication. |
