雷尼替丁产品中N-亚硝基二甲胺质量控制探讨

On the NDMA Quality Control of Ranitidine Products

目的:探索盐酸雷尼替丁类药品中N-亚硝基二甲胺(NDMA)产生的原因,分析雷尼替丁类产品存在的问题并提出建议,为雷尼替丁类药品生产企业和监管部门提供参考。方法:对230批次盐酸雷尼替丁类药品中NDMA检测结果进行统计分析;对雷尼替丁类药品生产企业进行调研,分析调研结果并提出建议。结果与结论:盐酸雷尼替丁原料药及胶囊中NDMA的含量偏高,这与药品生产过程中的温度、辅料及内包材、贮存环境密切相关。雷尼替丁类产品生产企业存在原料药中NDMA控制不严格、NDMA产生原因不明确、工艺变更困难等情况,因此企业应加强风险控制,提高原料药的入厂标准,持续进行工艺优化,减少盐酸雷尼替丁类药品中NDMA的产生。

Objective: To explore the causes of N-nitroso dimethylamine(NDMA) production in ranitidine hydrochloride drugs, analyze the problems existing in ranitidine hydrochloride products and put forward suggestions, so as to provide references for ranitidine drug manufacturers and regulatory authorities. Methods: The NDMA test results of 230 batches of ranitidine hydrochloride drugs were statistically analyzed;The ranitidine drug manufacturers were investigated, and the research results were analyzed and suggestions put forward. Results and Conclusion: The content of NDMA in ranitidine hydrochloride API and capsules is relatively high, which is closely related to the temperature, excipients, internal packing materials and storage environment. Ranitidine enterprises have some problems, such as the NDMA control is not strict, the cause of NDMA is not clear, and the process change is difficult, so enterprises should strengthen risk control, improve the factory entry standard of API, continuously optimize the process, and reduce the production of NDMA in ranitidine hydrochloride drugs.