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10d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。

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 salts.