高效液相色谱法测定阿哌沙班中的有关物质Determination of related substances in apixaban by HPLC
孙媛媛,赵云丽,段蒙蒙,王东凯,于治国
SUN Yuan-yuan,ZHAO Yun-li,DUAN Meng-meng,WANG Dong-kai,YU Zhi-guo
摘要(Abstract)：
目的建立高效液相色谱法定量测定阿哌沙班中有关物质。方法采用加校正因子的主成分自身对照法,对阿哌沙班中有关物质进行定量分析,并对该方法进行了方法学验证。结果杂质1、杂质2、杂质3、杂质4、杂质5及阿哌沙班的定量限分别为38.0、75.0、57.0、49.0、58.0和52.0μg·L~(-1);检测限分别为11.0、22.0、17.0、15.0、18.0和16.0μg·L~(-1)。各杂质的线性关系良好(r≥0.999),样品低、中、高三个水平的回收率均在90.0%~108.0%内,RSD≤4.0%。样品中杂质1含量质量分数为0.29%,最大未知单杂质含量质量分数为0.23‰,总杂质含量质量分数为0.31%。结论该方法可用于测定阿哌沙班中有关物质。
Objective To establish an HPLC method for the determination of related substances in apixaban.Method The self contrast and correction factor method was established to determine the related substances in apixaban simultaneously.Methods validation was also performed.Results The limits of quantitation for impurity 1,impurity 2,impurity 3,impurity 4,impurity 5 and apixaban were 38.0,75.0,57.0,49.0,58.0and 52.0 μg·L~(-1)respectively.And the limits of detection for impurities and apixaban were 11.0,22.0,17.0,15.0,18.0 and 16.0 μg·L~(-1)respectively.There was good linear relationship between response values and contents in the experimental concentration range of five impurities and apixaban(r≥0.999).The recovery ranged from 90.0% to 108.0% with RSD≤4.0%.The content of impurity 1 and unspecified impurity in the sample was 0.29% and 0.23‰,and the total impurities was 0.31%.Conclusions This method can be used to determine the related substances presented in apixaban.
关键词(KeyWords)：
阿哌沙班;有关物质;校正因子;高效液相色谱法
apixaban;related substance;correction factor;HPLC
基金项目(Foundation):
作者(Author):
孙媛媛,赵云丽,段蒙蒙,王东凯,于治国
SUN Yuan-yuan,ZHAO Yun-li,DUAN Meng-meng,WANG Dong-kai,YU Zhi-guo
DOI: 10.14066/j.cnki.cn21-1349/r.2017.01.007
参考文献(References)：
- [1]张先龙.新型口服抗凝药物阿哌沙班[J].中华关节外科杂志(电子版),2014,8(4):96-98.
- [2]刘俊,朱艳虹,栾家杰.临床药师参与心脏瓣膜置换术后华法林药物基因导向个体化抗凝治疗[J].中国医院药学杂志,2015,35(3):249-253.
- [3]GRANGER C B,ALEXANDER J H,MCMURRAY J J,et al.Apixaban versus warfarin in patients with atrial fibrillation[J].The NewEngland Journal of Medicine,2011,365(11):981-992.
- [4]JENNIFER C,JACK A.APIXABA N.An oral direct Factor Xa inhibitor:awaiting the verdict[J].Expert Opin Investig Drugs,2008,17(12):1937-1945.
- [5]ROSER-JONES C,BECKER R C.Apixaban:an emerging oral factor Xa inhibitor[J].J Thromb Thrombolysis,2010,29(1):141-146.
- [6]GRAEME J H,JOHN W E.Antithrombotic drugs for patients with ischaemic stroke and transient ischaemic attack to prevent recurrent major vascular events[J].Lancet Neurol,2010,9(3):273-284.
- [7]张震,孙燕.HPLC法测定阿哌沙班中的有关物质[J].天津药学,2014,26(6):9-11.
- [8]王忠波,李丹.RP-HPLC法测定阿哌沙班片的含量及有关物质[J].中国药房,2015,26(6):828-831.
- [9]张哲峰.HPLC法校正因子研究中的几个问题[EB/OL].(2011-12-07)[2013-01-13].http://www.cde.org.cn/dzkw.do?method=large Page&i d=312552.
- [10]国家食品药品监督管理总局.阿哌沙班片进口注册标准[S].标准号:JX20120076.
- [11]化学药物杂质研究的技术指导原则课题研究组.化学药物杂质研究的技术指导原则[M].北京:中国医药科技出版社,2005:1-16.