高效液相色谱法测定氟比洛芬酯注射液中11个有关物质的含量  

Determination of 11 related substances in flurbiprofen axetil injection by HPLC

作　　者：王雪 张小涵 李铁军 李文馨 李琳 杨书娟 张连义 窦艳丽 郭常川 徐玉文 WANG Xue;ZHANG Xiao-han;LI Tie-jun;LI Wen-xin;LI Lin;YANG Shu-juan;ZHANG Lian-yi;DOU Yan-li;GUO Chang-chuan;XU Yu-wen(Shandong Institute for Food and Drug Control,National Medical Products Administration(NMPA)Key Laboratory for Research and Evaluation of Generic Drugs,Shandong Research Center of Engineering and Technology for Consistency Evaluation of Generic Drugs,Industrial Technology Foundation Public Service Platform,Jinan 250101,China;Shandong Institute of Medical Device and Pharmaceutical Packaging Inspection,Jinan 250101,China;Jewim Pharmaceutical(Shandong)Co.,Ltd.,Taian 271000,China)

机构地区：[1]山东省食品药品检验研究院国家药品监督管理局仿制药研究与评价重点实验室山东省仿制药一致性评价工程技术研究中心产业技术基础公共服务平台,济南250101 [2]山东省医疗器械和药品包装检验研究院,济南250101 [3]山东京卫制药有限公司,泰安271000

出　　处：《药物分析杂志》2025年第2期246-253,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金项目(81973486,82173974);泰山产业领军人才工程专项经费资助项目(tscx202306073)。

摘　　要：目的:建立HPLC加校正因子的主成分外标法测定氟比洛芬酯注射液中11个杂质的含量,并对其检测结果及限度进行探讨。方法:采用Thermo BDS Hypersil Cis(250×4.6 mm,5μm)色谱柱,以含0.15%冰醋酸水溶液和含0.15%冰醋酸的乙睛为流动相进行梯度洗脱,流速1.0mL·min-l,柱温40℃,检测波长254nm,进样量10μL。结果:氟比洛芬酯及11个杂质均能有效分离,3-氟-4-苯基苯酚(4-0HB)1-乙酰氧基-2-(2-氟-4-联苯)-2-羟基丙酸酯(2-OHP)4-乙酰基-2-氟联苯(4-ACB)氟比洛芬乙酯、烯丙基-(2-氟-4-联苯)丙酸酯(ALE)《中华人民共和国药典》(ChP)杂质I、杂质B、杂质C与杂质E在0.10~20μg·mL-1质量浓度范围内与峰面积均呈良好的线性关系,r均为1.000,其平均回收率在96.6%~103.7%,RSD均不超过1.4%。4-0HB、2-0HP、4-ACB、氟比洛芬、氟比洛芬乙酯、ALE、ChP杂质I、杂质B、杂质C、杂质E的校正因子分别为0.55、1.05、1.01、0.76、0.95、0.86、0.55、0.93、0.76、0.81,氟比洛芬酯脱氟物检出结果在规定限度0.1%左右。结论:该方法快速、简便、准确、可靠,可用于氟比洛芬酯注射液有关物质的测定及质量控制。Objective:To establish a principal component external standard method with HPLC and calibration factors for the determination of 11 impurities in flurbiprofen axetil injection,and to explore its detection results and limit values.Methods:The Thermo BDS Hypersil Cis(250×4.6 mm,5μm)was selected for gradient elution,with water-0.15%acetic acid and acetonitrile-0.15%acetic acid as the mobile phase at a flow rate of 1.0 mL·min^(-1).The column temperature was 40 C,the detection wavelength was 254 nm and the injection volume was 10μL.Results:Flurbiprofen axetil and 11 impurities were well separated by the method.Good linearity was obtained with correlation coefficients of 1.000 for the 3-fluoro-4-phenylphenol(4-0HB),1-acetoxyethyl-2-(2-fluoro-4-biphenylyl)-2-hydroxypropionate(2-OHP),4-acetyl-2-fluorobiphenyl(4-ACB),flurbiprofen ethyl ester,allyl-(2-fluoro-4-biphenyl)propionate(ALE),ChP impurity I,impurity B,impurity C and impurity E in the range of 0.10-20μg·mL^(-1).The average recovery rates was from 96.6%to 103.7%and the relative standard deviations(RSDs)were lower than 1.4%.The correction factors of flurbiprofen axetil related substances 4-OHB,2-OHP,4-ACB,flurbiprofen,flurbiprofen ethyl ester,ALE,ChP impurity I,impurity B,impurity C and impurity E were 0.55,1.05,1.01,0.76,0.95,0.86,0.55,0.93,0.76 and 0.81,respectively.Notablely,desfluoro fiurbiprofen axetil of detected was around the prescribed limit 0.1%.Conclusion:The method above is rapid,simple,accurate,and reliable,and can be applied for the determination and quality control of related substances in flurbiprofen axetil injection.

关 键 词：氟比洛芬酯 有关物质 校正因子 氟比洛芬酯脱氟物 高效液相色谱 

分 类 号：R917[医药卫生—药物分析学]