β-内酰胺类抗生素聚合物杂质控制策略的形成与发展

Impurity control strategy ofβ-lactam antibiotics polymer:the formation and development

对聚合物杂质的分析是当前β-内酰胺类抗生素杂质谱控制的最薄弱环节。控制聚合物杂质源于人们对β-内酰胺类抗生素过敏反应的关注。伴随着β-内酰胺类抗生素过敏反应机制、聚合物结构和聚合机制等研究的深入,人们对β-内酰胺类抗生素聚合物的控制理念也逐渐成熟。采用专属的RP-HPLC方法,利用聚合物谱(polymer profile)评价生产工艺;同时,利用指针性聚合物控制聚合物的总量和工艺的稳定性,是控制β-内酰胺类抗生素聚合物的理想方案。利用强制聚合样品,通过二维色谱-MS联用技术,可以快速建立RP-HPLC聚合物谱分析方法,从技术上解决了聚合物谱控制的难题。但如何确定β-内酰胺类抗生素聚合物的质控限度问题仍需要进一步的思考。

Analysis ofβ-lactams antibiotics polymer impurities is the weakest aspect in the impurity profiling.Control of these impurities directly relate to the concerns about the anaphylaxis ofβ-lactam antibiotics.With the research progress of allergic reaction,polymer structure and polymerization mechanism,the concept for control ofβ-lactam antibiotics polymer impurities has become gradually matured.It is the ideal strategy to use polymer profile to evaluate the manufacture process and a pointer polymer to indicate the total polymer impurities,as well as control of the stability of production by RP-HPLC method.By two-dimensional chromatography-MS,the polymer profile analysis of RP-HPLC can be quickly established,solving the problem of polymer profile control.However,it still needs to be considered on how to determine the limit of the polymer for quality control.