摘要
目的：建立利伐沙班片的含量和有关物质的HPLC法。方法：采用RP-HPLC法测定利伐沙班片中利伐沙班的含量,并对其有关物质进行检测。色谱柱为Ultimate LP-C18（250 mm×4.6 mm,5μm）,乙腈-0.01 mol·L^-1磷酸溶液为流动相梯度洗脱,流速1.0 m L·min^-1,柱温30℃,检测波长250 nm;同时采用NP-HPLC法测定利伐沙班片中R-利伐沙班的含量,色谱柱为CHIRALPAKAD-H（250 mm×4.6 mm,5μm）,以甲基叔丁基醚-异丙醇-二乙胺（70∶30∶0.1）为流动相,流速0.8 m L·min^-1,柱温30℃,检测波长250 nm。结果：RP-HPLC法中主峰和相邻杂质峰能完全分离,利伐沙班的线性范围为0.009 6~0.167 mg·m L^-1,平均回收率（n=9）为99.7%;NP-HPLC法中R-利伐沙班与利伐沙班能完全分离,R-利伐沙班的线性范围为1.78~5.35μg·m L^-1,平均回收率（n=9）为100.7%。3批样品含量测定结果分别为99.1%、99.9%、100.2%,单个最大杂质分别为0.03%、0.06%、0.14%,总杂质分别为0.10%、0.13%、0.19%;3批样品中R-利伐沙班的含量分别为0.023%、0.021%、0.020%。结论：经方法学验证,本方法可用于利伐沙班片的质量控制。
Objective： To establish an HPLC method of the content and related substances of rivaroxaban tablets.Methods： RP- HPLC was adopted to determine rivaroxaban,related substances,content uniformity and dissolution using an Ultimate LP- C18 column（ 250 mm × 4. 6 mm,5 μm） with a gradient elution system of acetonitrile- 0. 01 mol·L- 1phosphoric acid,while the column temperature was maintained at 30 ℃,the flow rate was 1. 0 m L·min- 1and the detection wavelength was 250 nm. NP- HPLC was adopted to determine R- rivaroxaban in rivaroxaban tablets using an CHIRALPAK AD- H column（ 250 mm × 4. 6 mm,5 μm） with a mobile phase consisting of tert- butyl methyl ether- isopropanol- diethylamine（ 70∶ 30∶ 0. 1）. The column temperature was maintained at 30 ℃,the flow rate was 0. 8 m L·min- 1 and the detection wavelength was 250 nm. Results： Related substances were completely separated from the main constituents in RP- HPLC. The standard curve of rivaroxaban was linear over the range of 0. 009 6- 0. 167 mg·m L- 1,with the average recovery of 99. 7%（ n = 9）. R- rivaroxaban was completely separated from rivaroxaban in NP- HPLC. The standard curve of R- rivaroxaban was linear over the range of 1. 78- 5. 35 μg·m L- 1,with the average recovery of100. 7%（ n = 9）. The content results of 3 batches were 99. 1%,99. 9% and 100. 2%,respectively; the maximum single impurity was 0. 03%,0. 06% and 0. 14%,respectively; the total impurities were 0. 10%,0. 13% and 0. 19%,respectively.The content results of R- rivaroxaban in the 3 batches were 0. 023%,0. 021% and 0. 020% respectively. Conclusion：The method is proved by the methodology validation that it can be used for the quality control of rivaroxaban tablets.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2015年第4期699-704,共6页
Chinese Journal of Pharmaceutical Analysis
