目的 研究6種達比加群酯鹽在不同條件下的降解產(chǎn)物,尋找不同酸根與達比加群酯鹽穩(wěn)定性之間的相互關(guān)系。方法 將6種鹽在高溫、高濕和光照條件下分別放置10d后,利用HPLC和LC-MS法對不同鹽的降解產(chǎn)物進行深入分析。結(jié)果 通過LC-MS法解析得到達比加群酯鹽的3種關(guān)鍵降解產(chǎn)物,初步推斷出不同雜質(zhì)的產(chǎn)生與所選用的酸根結(jié)構(gòu)密切相關(guān)。結(jié)論 為了尋找更加穩(wěn)定的達比加群酯鹽,需要選用氧化還原性弱,結(jié)構(gòu)中含氧基團少及pKa值較低的酸根。

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.