001中二氯乙醇残留检测报告.docVIP

替硝唑中二氯乙醇残留测定报告 Report for Determination of Residual 2-Chloroethanol Oxide in Tinidazole 实施部门： 注册部QR组 负 责 人： 聂娟 日期： 2010年月日 姓名 Name 职责 Responsibility 部门 Department 签字及日期 Signature/Date 起草人 Written by QR组 黄国泉 审核人 Reviewed by QR组 聂娟 审核人 Reviewed by 陈霞娟 审核人 Reviewed by QA 周丽华 批准人 Approved by QA 生效日期 Effective date  1. 目的（Purpose） 。qualitative test of the starting material 2-Chloroethanol Oxide which is considered as a genotoxic substance. Which help us to determine whether it’s necessary to include the control of 2-Chloroethanol in the specification of Tinidazole. 2. 范围（Scope） 适用于测定。 in Tinidazole 3. 职责（Responsibility） QR: 负责实施QA：负责的审核及批准。 Responsibility QR: Responsible for the experiment implementation and report writing. QA: Responsible for the report audited and approved. 4. 内容（Content） 4.1. 基本信息(Basic information) 4.1.1根据欧洲药品管理局（EMEA）基因毒性杂质限度指南（Guideline On The Limits Of Genotoxic Impurities ）(EMEA/CHMP/QWP/251344/2006)，应对药品中潜在基因毒性杂质进行控制。基于结构警告（structural alerts） 替硝唑起始物料二氯乙醇含有潜在致癌性和/或基因毒性的基团： 化学名 结构式 用途 二氯乙醇 根据该指南，在缺少相关毒理学资料时，这些潜在基因毒性杂质的限度可按下式计算： 限度 (ppm) = TTC[μg/天] MDD[g/天] 其中TTC（Threshold of Toxicological Concern）为需要毒理学试验的阈值，为1.5μg/天； MDD（Maximal Daily Dose）为最大日剂量，替硝唑为2.0g/天。因此限度为0.75ppm。Basic information 4.1.1 Summarize According to the guideline on the limits of genotoxic impurities (EMEA/CHMP/ QWP QWP/251344/2006 )，the potential genotoxic substance in drug should be controlled. For the structural alerts of 2-Chloroethanol, It is considered as a genotoxic substance Chemical name structure application 2-Chloroethanol Make the starting material According to the guildline, the limitation of the genotoxic substance can be calculated by the following formula when less of the related material of toxicology. Limitation (ppm) = TTC[μg/day] MDD[g/day] In which TTC is the Threshold of toxicological Concem (1.5μg/day); MDD is the maximal daily dose, the MDD for Tinidazole is 2.0g/day. So the limitation