实验研究达比加群酯盐的降解产物研究.PDFVIP

现代药物与临床 Drugs Clinic 第 31 卷 第 5 期 2016 年 5 月 ·567 · • 实验研究 • 达比加群酯盐的降解产物研究 1, 2 2 2 2* 2 2 2* 宗新杰 ，李 川 ，付晓丽 ，张海枝 ，刘长鹰 ，刘 鹏 ，徐为人 1. 天津中医药大学，天津 300193 2. 天津药物研究院 天津市药物设计与发现重点实验室，天津 300193 摘 要：目的 研究 6 种达比加群酯盐在不同条件下的降解产物，寻找不同酸根与达比加群酯盐稳定性之间的相互关系。 方法 将 6 种盐在高温、高湿和光照条件下分别放置 10 d 后，利用 HPLC 和 LC-MS 法对不同盐的降解产物进行深入分析。 结果 通过 LC-MS 法解析得到达比加群酯盐的 3 种关键降解产物，初步推断出不同杂质的产生与所选用的酸根结构密切相 关。结论 为了寻找更加稳定的达比加群酯盐，需要选用氧化还原性弱，结构中含氧基团少及 pKa 值较低的酸根。 关键词：达比加群酯；降解产物；酸根；稳定性 中图分类号：R914 文献标志码：A 文章编号：1674 - 5515(2016)05 - 0567 - 05 DOI: 10.7501/j.issn.1674-5515.2016.05.001 Degradation products of dabigatran etexilate salts 1, 2 2 2 2 2 2 2 ZONG Xin-Jie , LI Chuan , FU Xiao-li , ZHANG Hai-zhi , LIU Chang-ying , LIU Peng , XU Wei-ren 1. Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China 2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China Abstract: Objective To study the degradation products of six different dabigatran etexilate salts under various condition and find the correlation between selected acids and the stability of salts. Methods Six different dabigatran etexilate salts were placed under high temperature, high humidity or illumination for 10 d. Then, the degradation products were detailedly analyzed by HPLC and LC-MS methods. Results Three important degradation products were analyzed, and the close relation between its generation and the structure of selected acid was deduced. Conclusion The acid with weak reducing property, fewer oxygen-contained groups and lower pKa could be applied to form more stable dabigatran etexilate sal