中国药物警戒 ›› 2024, Vol. 21 ›› Issue (8): 852-856.
DOI: 10.19803/j.1672-8629.20240375

• 细菌内毒素检测技术与实践专栏 • 上一篇    下一篇

右旋兰索拉唑原料药的细菌内毒素检查方法研究

徐美宝1, 裴宇盛2△, 陈晨2, 李文龙2, 刘涛3, 蔡彤2,*   

  1. 1天津市天大天发科技有限公司,天津 300392;
    2中国食品药品检定研究院化学药品检定所,北京 102629;
    3中国科学院苏州生物医学工程技术研究所,江苏 苏州 215163
  • 收稿日期:2024-05-31 出版日期:2024-08-15 发布日期:2024-08-21
  • 通讯作者: *蔡彤,女,硕士,主任药师,药品质量控制。E-mail: teddyct@163.com
  • 作者简介:徐美宝,男,本科,副高级工程师,药品分析化验。△为并列第一作者。
  • 基金资助:
    国家重点研发计划（2023YFC2606100）

Bacterial endotoxin test of (R)-lansoprazole raw material

XU Meibao1, PEI Yusheng2△, CHEN Chen2, LI Wenlong2, LIU Tao3, CAI Tong2,*   

  1. 1TIANDA TIANFA-Pharmaceutical Testing Instrument Manufacturer, Tianjin 300392, China;
    2National Institute for food and drug control Institute for Chemical Drug Control, Beijing 102629, China;
    3Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences, Suzhou Jiangsu 215163, China
  • Received:2024-05-31 Online:2024-08-15 Published:2024-08-21

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摘要： 目的 为难溶性原料药右旋兰索拉唑建立细菌内毒素检测方法。方法 使用3种方法建立右旋兰索拉唑的内毒素检查方法。①乙腈溶解供试品至10 mg·mL-1,稀释100倍,使用凝胶法、灵敏度为0.25 EU·mL-1的鲎试剂进行检测;②使用1.4 mg·mL-1氢氧化钠溶解样品至10 mg·mL-1,稀释600倍,使用凝胶法、灵敏度为0.03 EU·mL-1的鲎试剂进行细菌检测;③使用三氯甲烷溶解供试品,然后采用萃取的方法进行内毒素检测。结果 3批供试品使用乙腈和1.4 mg·mL-1氢氧化钠溶液溶解样品后采用检查用水稀释的方法,均可排除溶剂及供试品对细菌内毒素检测的干扰,干扰试验结果符合要求,且供试品细菌内毒素含量小于限值。符合《中华人民共和国药典》（2020年版）规定。但三氯甲烷萃取的方法存在较大干扰,结果不成立。结论 建立右旋兰索拉唑原料药的细菌内毒素检测方法,解决了样品的检测难点,为其他难溶性样品建立细菌内毒素检测方法提供参考。

关键词: 右旋兰索拉唑, 原料药, 细菌内毒素, 凝胶法, 乙腈, 三氯甲烷, 氢氧化钠溶液

Abstract: Objective To establish a bacterial endotoxin detection method for the poorly soluble active pharmaceutical ingredient (R)-Lansoprazole. Methods Three methods were attempted to establish the bacterial endotoxin detection method.① The test sample was dissolved in acetonitrile to a concentration of 10 mg·mL-1, diluted 100-fold, and tested using the gel-clot method with a lysate sensitivity of 0.25 EU·mL-1. ② The sample was dissolved in 1.4 mg·mL-1 sodium hydroxide solution to a concentration of 10 mg·mL-1, diluted 600-fold, and tested for bacterial endotoxins using the gel-clot method with a lysate sensitivity of 0.03 EU·mL-1.③ Dissolve the test sample in chloroform, and then perform endotoxin detection using extraction method. Results For all three batches of test samples, dissolving the samples in both acetonitrile and 1.4 mg·mL-1 sodium hydroxide solution then diluted by water for bacterial endotoxin test, could eliminate the interference of the solvent and test sample on endotoxin detection. The results of the interference test meet the requirements. The endotoxin content of the test samples was found to be below the limit and in compliance with the pharmacopoeia requirements. However, the chloroform extraction method has significant interference and the results are not valid. Conclusion A bacterial endotoxin detection method for the active pharmaceutical ingredient (R)-Lansoprazole is successfully established, which solves the detection problem of this sample and provides a reference for establishing bacterial endotoxin detection methods for other insoluble samples.

Key words: (R)-lansoprazole, raw material, bacterial endotoxin, gel method, acetonitrile, trichloromethane, sodium hydroxide solution

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