【摘要】 目的建立反相高效液相色谱法测定丁酸氯维地平原料药的含量及其有关物质,并用所建立的方法测定其水溶液的稳定性及油水分配系数。方法丁酸氯维地平含量测定采用Prodigy ODS C18色谱柱(150 mm×4.6 mm,5μm),以水-乙腈(体积比55∶45)等度洗脱,柱温30℃,流速1.0 mL·min-1,检测波长238 nm。有关物质采用体积分数0.05%三乙胺(磷酸调pH值至3.0)-乙腈-甲醇(体积比40∶40∶20)为流动相等度洗脱,主成分自身对照法检查。配制不同pH值的磷酸缓冲溶液测定其水中稳定性,采用摇瓶法测定其油水分配系数。结果含量测定条件重复性好(RSD=0.2%),平均回收率为100.2%,RSD为0.5%(n=9),经测定3批原料药的含量质量分数分别为99.8%、99.8%和99.7%,有关物质含量均低于限度(0.5%),丁酸氯维地平在水中按一级动力学降解并具有较强亲脂性。结论本法专属性强、准确、灵敏,能满足丁酸氯维地平原料药的质量控制要求。更多还原

【Abstract】 Objective To establish an RP-HPLC method for the determination of clevidipine butyrate( CDB) and its related substances. To determine the distribution coefficient of CDB betw een octanol / distilled w ater and research the stability of CDB in buffers w ith different pH. Methods The separation w as performed on a Prodigy C18column( 150 mm × 4. 6 mm,5 μm) and the mobile phase w as w ater-acetonitrile( V ∶ V = 55∶ 45) at the flow rate of 1. 0 mL·min- 1. The column temperature w as 30 ℃ and the w avelength w as set at 238 nm. For the content determination,the mobile phase w as triethylamine aqueous solution w ith a volume fraction of 0. 05%( adjusted to 3. 0 w ith phosphoric acid)-acetonitrile-methanol( V ∶ V ∶ V = 40∶ 40∶ 20),and the related substances w ere tested by the method of 0. 5% reference solution corresponding impurities. The distribution coefficient of CDB betw een octanol / distilled w ater w as determined by shaking flask method. Results For the content determination,the repeatability was good with RSD of 0. 2%. The average recovery w as 100. 2%( n = 9). The contents in three batches of samples w ere 99. 8%,99. 8% and 99. 7%,respectively,and the contents of their related substances w ere all under the limitation. The degradation of clevidipine butyrate in aqueous solution at different pH values follow ed first-order kinetics,and it w as lipophilic. Conclusions This method is specific,accurate and sensitive,and it is applicable for the quality control of CDB.更多还原