匹伐他汀钙光降解杂质的合成

Synthesis of photodegradation impurities from pitavastatin calcium

目的合成匹伐他汀钙光降解杂质。方法以匹伐他汀钙为原料,经盐酸中和制得匹伐他汀。匹伐他汀经氧化、成盐得匹伐他汀钙5-酮体(1);匹伐他汀经内酯化、光环化、水解、成盐得匹伐他汀钙闭环体(2)。结果两个光降解杂质的结构经核磁共振氢谱、碳谱、氟谱、DEPT谱和高分辨率质谱确证,纯度经HPLC检测均在99.0%以上。结论合成的两个杂质可以作为匹伐他汀钙原料药及其制剂质量控制的杂质对照品。

Objective To synthesis the two pitavastatin calcium photodegradable impurities.Methods Pitavastatin was prepared from pitavastatin calcium salt with hydrogen chloride.Pitavastatin calcium 5-keto form(1)was prepared from pitavastatin via oxidation and salinization.Pitavastatin calcium ring-closed form(2)was prepared from pitavastatin via lactonization,photocyclization,hydrolysis and salinization from pitavastatin.Results The chemical structures of the two photodegradable impurities were confirmed by 1H NMR,13C NMR,19F NMR,DEPT and HRMS.The purities were over 99.0%as determined by HPLC.Conclusion The synthesized two impurities can be used as the reference substances for the quality control of pitavastatin calcium and its preparations.