复方盐酸替利定口服液中主要杂质的结构确证与工艺改进-中国药事.PDFVIP

中国药事 2018年5月 第32卷 第5期 603 ·药物研究· 复方盐酸替利定口服液中主要杂质的结构确证与 工艺改进 蒋晓磊，焦正花 （甘肃省中医院， 兰州 730000） 摘要 ：目的 研究复方盐酸替利定口服液主要杂质的结构和产生的原因，提高复方替利定口服液的质量。 方法：通过 LC-MS、IR 和 H-NMR 检测分析其可能的结构并通过分离、合成等方法对杂质结构进行确 认，从而在合成工艺上作出相应改进，减少杂质的含量。结果：按照选定方法，获得复方盐酸替利定口 服液三个主要杂质（顺式替利定、反式去甲替利定和顺式去甲替利定），并与 LC-MS、IR、H-NMR 结果一一对应。以此依据在合成工艺方面做出了相应改进，减少了盐酸替利定原料杂质的含量，从而提 高了复方替利定口服液的质量。结论：本研究提高了盐酸替利定原料的纯度，进一步对提高复方盐酸替 利定口服液的质量具有一定价值。 关键词： 盐酸替利定；复方盐酸替利定口服液；镇痛药；杂质；结构确证；工艺改进 R927 A 1002-7777(2018)05-0603-08 中图分类号： 文献标识码： 文章编号： doi:10.16153/j.1002-7777.2018.05.006 Structure Confirmation and Technology Improvement of Main Impurities of Compound Tilidine Hydrochloride Oral Solution Jiang Xiaolei, Jiao Zhenghua (Gansu Provincial Hospital of TCM, Lanzhou 730000, China ) Abstract Objective: To analyze the structure and causes of the main impurities so as to improve the quality of compound tilidine hydrochloride oral solution. Methods: The structure of the main impurities was analyzed by LC-MS, IR and H-NMR, then the structure of the impurities was confirmed with separation and synthesis methods so that the synthetic technology was improved to reduce the impurities. Results: By using the selected methods, three main impurities of compound tilidine hydrochloride oral solution (cis-tigridine, trans-nortanilidine and cis- formitridine) were obtained in correspondence with the results of LC-MS, IR and H- NMR. Based on the results, the synthetic technology was improved to reduce the impurities of raw material of tilidine hydrochloride and it has improved the quality of compound tilidine hydrochloride oral solution. Conclusion: In this study, the purity of raw material of tilidine hydrochloride was improved, which was valuable in improving the quality of compound tilidine hydrochloride oral solution. Keywords tilidine hydrochloride; compound tilid