HPLC-DAD可变波长法测定甲磺酸达比加群酯原料药中10种已知杂质的含量  

Determination of related substances in dabigatranetexilatemesylate by HPLC-DAD

作　　者：郭萍[1] 高爽[1] 孙丽娇 陈明明[2] 陈晓辉[1] GUO Ping;GAO Shuang;SUN Lijiao;CHEN Mingming;CHEN Xiaohui(School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;Institute for Drug and Instrument Control of Shenyang Military Area Command, Shenyang 110026, China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]沈阳军区药品仪器检验所,辽宁沈阳110026

出　　处：《沈阳药科大学学报》2018年第5期384-389,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立HPLC-DAD法同时测定甲磺酸达比加群酯原料药中10种已知杂质的含量。方法采用YMC C18(150 mm×4.6 mm,5μm)色谱柱,以乙腈-20 mmol·L-1磷酸二氢钾水溶液(用磷酸调节p H值至4.1)梯度洗脱并采用多波长检测(242、310和340 nm),流速为0.6 m L·min-1,柱温40°C,进样量5μL。结果甲磺酸达比加群酯与各杂质能达到基线分离。杂质1~10的质量浓度分别在0.160~2.99 mg·L-1、0.069~1.98 mg·L-1、0.107~2.00 mg·L-1、0.060~1.99 mg·L-1、0.072~4.04 mg·L-1、0.166~2.01 mg·L-1、0.078~2.00 mg·L-1、0.157~2.00 mg·L-1、0.159~2.00 mg·L-1和0.072~4.00 mg·L-1内与各自峰面积积分值呈良好的线性关系(r分别为0.995 1、0.997 8、0.997 3、0.997 9、0.995 0、0.998 2、0.997 5、0.999 7、0.996 6、0.9971);平均加样回收率在99.5%~102.7%内。在三个不同批次的原料药中只检测到了杂质5、6和10,测得三个批次中的最大单杂含量分别为0.059%、0.058%和0.056%,杂质总量分别为0.16%、0.16%和0.16%。结论本方法可用于达比加群酯中已知杂质的定量检查。Objective To develop a method to determine the content of 10 kinds of known related substances of dabigatranetexilatemesylate. Methods Separations were carried out with an YMC C18（ 150 mm × 4. 6 mm,5 μm） analytical column,which was maintained at 30 ℃. The mobile phase was consisted of 20 mmol·L-1 aqueous potassium dihydrogen phosphate（ the p H was adjusted to 4. 10 with phosphoric acid） and acetonitrile. The flowrate was 0. 6 m L·min-1. Analytes were detected at λ = 242 nm,310 nm and 340 nm by diode array detector（ DAD）,respectively. Results The developed method had a good separation between the impurities and the main peak,under the chromatographic conditions of the relevant substances. the calibration curves were linear in the range of 0. 160-1. 996 μg·m L-1（ impurity 1）,0. 060-1. 980 mg·L-1（ impurity2）,0. 107-2. 004 mg·L-1（ impurity 3）,0. 050-1. 988 mg·L-1（ impurity 4）,0. 072-2. 020 mg·L-1（ impurity 5）,0. 170-2. 012 mg·L-1（ impurity 6）,0. 077-1. 996 mg·L-1（ impurity 7）,0. 160-2. 008 mg·L-1（ impurity 8）,0. 150-2. 008 mg·L-1（ impurity 9） and 0. 060-2. 004 mg·L-1（ impurity 10）with a good precision（ least squares regression coefficients were varied from 0. 997 8 to 0. 999 7）. The recoveries of impurities were varied from 99. 5% to 102. 65%. The method precisions were 0. 91%,1. 09%,1. 22%,1. 35% and 1. 18%,respectively. Impurities 1,5,6 and 10 were detected in three different batches of APIs,and the total amount of impurities were 0. 15%,0. 16%,0. 16%,respectively. Conclusion The correction factor method is simple,accurate and reliable,and it is suitable for the control of related substances in dabigatranetexilate. Accordingly,it provides the basis for the quality control of dabigatranetexilate.

关 键 词：达比加群酯 已知杂质 HPLC-DAD 

分 类 号：R917[医药卫生—药物分析学]