西罗莫司胶囊有关物质测定方法的改进

Improved analysis of related substances of sirolimus capsules

目的改进西罗莫司胶囊现行标准中有关物质的测定方法,为合理评价其质量提供依据。方法从西罗莫司的生物合成途径及分子结构等出发预测西罗莫司主要的工艺杂质及降解杂质,通过色谱条件的筛选和优化分别建立了可同时测定开环降解杂质和工艺杂质的有关物质1分析方法并新建了单独控制氧化降解杂质的分析方法。结果新建的方法可弥补现行标准不能有效控制制剂工艺及储藏过程中可能产生的开环降解杂质和氧化物杂质的缺陷,利于企业监测产品的质量,进而提高临床用药的安全性。结论新建的有关物质测定方法专属性、耐用性和重复性良好,可更加有效地评价产品的质量。

Objective To improve the analysis method of the related substances of sirolimus capsules, and evaluate the quality reasonably. Methods According to the biosynthetic pathway and the structure of sirolimus, we predicted its processed impurities and degradation impurities. The controlling methods were established through a series of chromatographic optimization. Results The new methods can make up the defections of the detection and the controlling of degradation impurities such as the open-ring and oxidation products, which were generated during pharmaceutical processes or/and storage. The new methods were beneficial for monitoring the quality of the products, and improving the safety of the clinical treatment. Conclusion The new methods are specific, durable and reproducible, and it can evaluate the quality of sirolimus capsules more effectively.