高效液相色谱法测定富马酸比索洛尔原料药及其制剂中的有关物质  

Determination of related substances in bisoprolol fumarate raw materials and its preparations by HPLC

作　　者：程智 王孝艳 雍子宜 谢华 CHENG Zhi;WANG Xiao-yan;YONG Zi-yi;XIE Hua(Sichuan Institute of Drug Control,Chengdu 611731;School of Pharmacy,Chengdu Medical College,Chengdu 610500)

机构地区：[1]四川省药品检验研究院,成都611731 [2]成都医学院药学院,成都610500

出　　处：《中南药学》2021年第7期1405-1410,共6页Central South Pharmacy

基　　金：国家药典委员会国家药品标准提高研究项目(食药监办药化管[2019]141号)。

摘　　要：目的建立HPLC法测定富马酸比索洛尔原料药及其制剂中的有关物质。方法采用色谱柱Kromasil C_(18)(4.6 mm×250 mm,5μm),流动相A为磷酸盐缓冲液(称取磷酸二氢铵3.45 g,加水900 mL,磷酸调节pH值至2.5,加水至1000 mL),流动相B为磷酸盐缓冲液-乙腈(20∶80),梯度洗脱,流速1.0 mL·min^(-1),检测波长225 nm,柱温30℃,进样量20μL。结果富马酸、杂质A、杂质羟乙酯、杂质L、杂质酸、比索洛尔、杂质G、杂质K、杂质M、杂质N-醛依次出峰,各峰间的分离度良好,均大于1.5;空白溶剂、片剂及胶囊辅料均不干扰8个已知杂质的检测,杂质A、杂质G、杂质K、杂质L、杂质M、杂质N-醛、杂质羟乙酯、杂质酸和比索洛尔的定量限分别为0.152、0.246、0.286、0.268、0.216、0.241、0.214、0.257和0.159μg·mL^(-1),平均回收率在90.45%~108.82%,RSD均小于3%。结论该方法灵敏度高,专属性好,可用于富马酸比索洛尔原料药、片剂和胶囊中有关物质的定量研究。Objective To determine the impurities and related substances in bisoprolol fumarate and its preparations by HPLC.Methods The separation was performed on Kromasil C_(18)(4.6 mm×250 mm,5μm)column with mobile phase A consisting of phosphate buffer solution(3.45 g ammonium dihydrogen phosphate,900 mL water,adjustinig pH value to 2.5 with phosphoric acid,and adding water to 1000 mL),while mobile phase B consisting of phosphate buffer solution-acetonitrile(20∶80),gradient elution at the flow rate of 1.0 mL·min^(-1).The detection wavelength was 225 nm,the column temperature was 30℃and the injection volume was 20μL.Results Fumaric acid,impurity A,impurity hydroxyethyl ester,impurity L,impurity acid,impurity bisoprolol,impurity G,impurity K,impurity M and impurity N-aldehyde showed peaks in turn,and the separation degree between each peak was greater than 1.5.The blank solvent,excipients in both tablets and capsules did not interfere with the detection of the 8 known impurities.The quantitation limits of impurities A,G,K,L,M,N-aldehyde,hydroxyethyl ester,acid and bisoprolol were 0.152,0.246,0.286,0.268,0.216,0.241,0.214,0.257 and 0.159μg·mL^(-1),respectively.The average recoveries ranged from 90.45%to 108.82%,with RSD less than 3%.Conclusion The method is sensitive and specific,and can be used for the quantitative study of related substances in bisoprolol fumarate bulk drugs,tablets and capsules.

关 键 词：富马酸比索洛尔 有关物质 高效液相色谱法 

分 类 号：R927[医药卫生—药学]