β-内酰胺酶抑制剂的稳定性与降解反应特性

Stability and degradation characteristics ofβ-lactamase inhibitors

β-内酰胺酶抑制剂与广谱β-内酰胺抗生素的联合使用是一种有效解决细菌耐药的策略之一。目前上市的β-内酰胺酶抑制剂按其化学结构主要包括氧青霉烯类(克拉维酸)、青霉烷砜类(舒巴坦和他唑巴坦)和二氮杂二环辛烷类化合物(阿维巴坦),本文对临床常见的β-内酰胺酶抑制剂的稳定性与降解反应特性进行综述,并结合当前药典标准中的有关物质检查项,探讨上述β-内酰胺酶抑制剂的杂质谱控制策略。

The combination ofβ-lactamase inhibitors with broad-spectrumβ-lactam antibiotics is one of the effective strategies to meet the challenge of bacterial resistance.Currently,β-lactamase inhibitors mainly used on the market include oxapenems(clavulanic acid),penicillane sulfones(sulbactam and tazobactam)and diazabicyclooctanes(avibactam),according to their chemical structure.In this paper,the stability and degradation mechanisms/characteristics of theβ-lactamase inhibitors were reviewed.Combined with the methods of related substance determination in the specifications of pharmacopeia,the strategy for the impurity profiling control of theβ-lactamase inhibitors was discussed.