摘要
康替唑胺(Contezolid)由中国自主研发并拥有全球知识产权,首个在中国上市的国产原研噁唑烷酮类抗菌新药,在新药研发阶段,元素杂质的研究和控制是确保药品安全和质量的关键环节。由于康替唑胺本身物理化学性质及其片剂包含很多难溶的辅料,因此在样品前处理过程中需考虑样品消解完全和稳定汞离子,本文采用HNO_(3)/HCl/HF(6:1:0.1)微波消解,用混合酸(H_(2)O/HNO_(3)/HCl(95:4:1))稀释解决了上述问题,根据USP<233>获得了良好的方法验证结果,建立了康替唑胺原料药和片剂中12种元素杂质的检测方法,根据实际样品的检测结果对康替唑胺片进行元素杂质风险评估,以确保该药品元素杂质符合ICH Q3D规定。
Contezolid is a novel oxazolidinone antibacterial drug independently developed in China with global intellectual property rights,and it is the first domestically developed original drug of this class to be marketed in China.During the drug development phase,the research and control of elemental impurities are crucial for ensuring the safety and quality of the drug.Given the physicochemical properties of Contezolid itself and the presence of many poorly soluble excipients in its tablet formulation,it is necessary to consider complete sample digestion and stabilization of mercury ions during the sample pretreatment process.In this study,a microwave digestion method using HNO_(3)/HCl/HF(6:1:0.1)was employed,and the sample was diluted with a mixed acid(H_(2)O/HNO_(3)/HCl/HF(95:4:1))to address the above issues.Based on USP<233>,good method validation results were obtained,and a detection method for 12 elemental impurities in Contezolid API and tablets was established.An elemental impurity risk assessment of Contezolid tablets was conducted based on the actual sample test results to ensure that the elemental impurities in the drug comply with the ICH Q3D guidelines.
作者
邹文博
李芯瑶
朱俐
ZOU Wen-bo;LI Xin-yao;ZHU Li(NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,National Institutes for Food and Drug Control,Beijing 102629,China;School of Pharmacy,China Pharmaceutical University,Nanjing 510240,China)
出处
《化学研究与应用》
北大核心
2025年第9期2829-2834,共6页
Chemical Research and Application
关键词
康替唑胺
电感耦合等离子体质谱
元素杂质
风险评估
Contezolid
Inductively Coupled Plasma Mass Spectrometry(ICP-MS)
Elemental Impurities Risk Assessment
