目的 结合相关文献、专利和人用药品注册技术要求国际协调会(ICH)M7指南,提出阿哌沙班杂质控制的基础策略,旨在为进行该品种仿制药杂质研究工作提供参考。方法 阿哌沙班及其制剂是目前仿制药申报较为热门的品种,阿哌沙班合成过程中可能产生或残留较多的致突变杂质,系该品种仿制制剂研制的关注重点。笔者对阿哌沙班有机杂质谱进行分析,重点关注潜在致突变杂质控制。结果与结论 结合阿哌沙班合成路线、物料特性和ICH M7指南对阿哌沙班潜在的致突变杂质分析及控制进行了讨论。致突变杂质控制是该产品质量控制的重要内容之一,应结合清除跟踪研究数据,建立科学的控制策略。
Abstract
OBJECTIVE To discuss basic strategies for impurity control of apixaban combining with the relevant literatures, patents, and ICH M7 guidelines, in order to give some advices on the comprehensive research of impurities of generic drugs of apixaban. METHODS Apixaban and apixaban tablets are hot points in application of generic drugs in recent years.The research of genotoxic impurities involved in the synthesis of apixaban is the key point in generics research. In the article, the analysis and control of potential impurities were discussed, focusing on the control of the genotoxic impurities. RESULTS AND CONCLUSION The analysis and control of apixaban′s potential genotoxic impurities were discussed based on the synthetic route, material characteristics of apixaban and ICH M7 guidelines. The control of genotoxic impurities is one of the important contents of the quality control of apixaba. A scientific control strategy should be established in conjunction with the removal and tracking research of the impurities.
关键词
阿哌沙班 /
杂质谱 /
致突变杂质 /
杂质控制
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Key words
apixaban /
impurity profile /
genotoxic impurity /
quality control impurity
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中图分类号：
R917
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参考文献
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