中国药物警戒 ›› 2016, Vol. 13 ›› Issue (12): 730-732.

• 质量与工艺研究 • 上一篇    下一篇

盐酸氟西汀有关物质的制备工艺优化研究

刘博1, 王腾1, 吴迪1, 2, 逄瑜3, 宋永吉1*, *   

  1. 1 北京石油化工学院化学工程学院,北京 102607;
    2 北京化工大学化学工程学院,北京 100029;
    3 国家食品药品监督管理总局药品评价中心,北京 100045
  • 收稿日期:2017-01-13 修回日期:2017-01-13 出版日期:2016-12-20 发布日期:2017-01-13
  • 通讯作者: 宋永吉,男,博士,教授·硕导,化学合成工艺研究。E-mail：yongjisong@bipt.edu.cn
  • 作者简介:刘博,男,博士,讲师,药物化学。
  • 基金资助:
    北京市教委科研计划一般项目（KM201610017004）

Research on Preparation Process Optimizing of Fluoxertine Hydrochloride Impurity

LIU Bo1, WANG Teng1, WU Di1, 2, PANG Yu3, SONG Yong-ji1, *   

  1. 1 Chemical Engineering College, Beijing Institute of Petrochemical Technology, Beijing 102607, China;
    2 Chemical Engineering College, Beijing University of Chemical Technology, Beijing 100029, China;
    3 Center of Drug reevaluation, CFDA, Beijing 100045, China
  • Received:2017-01-13 Revised:2017-01-13 Online:2016-12-20 Published:2017-01-13

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摘要： 目的 通过对盐酸氟西汀的有关物质制备工艺的系统优化,建立一种能够快速高效制备盐酸氟西汀有关物质Ⅲ的方法。方法 通过对多因素的化学反应条件（包括反应温度、反应浓度、反应体系酸碱性等）进行考察,借助核磁共振氢谱与高分辨质谱对最终产物结构进行确证,最终得到最优工艺条件。结果 经优化得到的盐酸氟西汀有关物质Ⅲ盐酸盐的工艺为连续一釜制备方法,总收率为82.05%。结论 建立了一种快速高效制备《中国药典》2015版盐酸氟西汀有关物质项下杂质Ⅲ（N-甲基-3-苯丙胺）盐酸盐的工艺路线,为盐酸氟西汀的毒理机制研究、质量标准提高以及降低不良反应等研究奠定了基础。

关键词: 盐酸氟西汀, 盐酸氟西汀杂质Ⅲ, 工艺优化, 有关物质

Abstract: Objective To develop a rapid and effective method for preparation of the fluoxertine hydrochloride related substanceⅢ in ChP 2015 by optimizing the preparation process. Methods Via verification of multiple factors (temperature, concentration and pH condition) and structure confirmation by NMR and HR-MS, finally, the optimum condition was founded. Results The process was an one-pot continuous method, the total yield was 82.05%. Conclusion An effective and rapid preparation route to synthesize compound hydrochloride N-menthyl-3-benzedrine was developed, which is the fluoxertine hydrochloride related substanceⅢ in ChP 2015. It also laid a foundation for the study of toxic mechanism, quality specification improvement and adverse reaction reducing of fluoxertine hydrochloride.

Key words: fluoxertine hydrochloride, fluoxertine hydrochloride impurity Ⅲ, process optimizing, related substance

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