对β-内酰胺抗生素中微量不稳定杂质研究策略与方法的思考

Reflection on strategy and methods on trace unstable impurities of β-lactam antibiotics

对药品中杂质的控制是保证药品用药安全的重要环节。β-内酰胺抗生素由于自身结构的不稳定,使得产品中杂质种类复杂、含量较低且结构不稳定,通常难以采用常规的方法进行研究。本文在已有的杂质研究相关指导原则的基础上,针对β-内酰胺抗生素中微量不稳定杂质的特点及研究中涉及的特殊问题,结合对β-内酰胺类抗生素杂质研究的实践经验,对研究中共性的策略与方法进行了讨论。

The safety of drug therapy is closely related to the quality of drugs.The impurity profiling has become the most important activity in assuring the high quality of drugs.However,the impurity profiles of β-lactam antibiotics are found with a great multiplicity as the structure of β-lactams is unstable,which made it difficult to use routine methods.Based on published technical requirements and guidance,and combining our experience,we discussed the strategy and technique used in impurity profiling study on trace unstable impurities in β-lactam antibiotics with emphasis on impurity determination,impurity identification as well as impurity qualification.