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 C18（250×4.6 mm,5 μm）色谱柱,以含0.15%冰醋酸水溶液和含0.15%冰醋酸的乙腈为流动相进行梯度洗脱,流速1.0 mL · min-1,柱温40 ℃,检测波长254 nm,进样量10 μL。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-OHB）、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0.10~20 μg · 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-OHB、2-OHP、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。
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
. 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*[J]. 药物分析杂志, 2025
, 45(2)
: 246
-253
.
DOI: 10.16155/j.0254-1793.2024-0489
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 C18 (250×4.6 mm, 5 μm) 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 ℃, the detection wavelength was 254 nm and the injection volume was 10 μL.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-OHB), 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 0.10-20 μg · 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.
[1] HAO J,WANG K,SHAO Y,et al.Intravenous flurbiprofen axetil to relieve cancer-related multiple breakthrough pain:a clinical study[J].J Palliat Med,2013,16(2):190
[2] 王天兵,姜保国,杨惠林,等.氟比洛芬巴布膏治疗骨科急慢性疼痛的多中心临床研究[J].中日友好医院学报,2013,27(1):18
WANG TB,JIANG BG,YANG HL,et al.Multicentre clinical research on flurbiprofen cataplasm for treating acute and chronic pain[J].J China Japan Friendship Hosp,2013,27(1):18
[3] 王统杰. 氟比洛芬巴布膏治疗急性软组织损伤的临床观察[J].中国医学工程,2013,21(6):37
WANG TJ.Clinical observation of flurbiprofen Babu ointment in the treatment of acute soft tissue injury[J].Chin Med Eng,2013,21(6):37
[4] 章秀丽,马月琴,李刚.脂微球载药系统的研究进展[J].药学实践杂志,2014,32(6):409
ZHANG XL,MA YQ,LI G,et al.Research development of lipid microsphere delivery system[J].J Pharm Pract,2014,32(6):409
[5] 吴燕,李冬梅,徐超斗,等.氟比洛芬酯脂微球注射液的制备及其质量评价[J].中国药学杂志,2013,48(21):1847
WU Y,LI DM,XU CD,et al.The preparation and evaluation of flurbiprofen axetil lipid microsphere injection[J].Chin Pharm J,2013,48(21):1847
[6] YAMASHITA K,FUKUSAKI M,ANDO Y,et al.Preoperative administration of intravenous flurbiprofen axetil reduces postoperative pain for spinal fusion surgery[J].J Anesth,2006,20(2):92
[7] 林赳杨. 氟比洛芬酯注射液的术后镇痛效果分析[J].现代诊断与治疗,2012,23(2):2
LIN JY.Analgesic effect and safety evaluation of flurbiprofen axetil injection in abdominal surgery[J].Pract J Clin Med,2012,23(2):2
[8] WANG RD,SHENG XR,GUAN WX,et al.Flurbiprofen axetil for postoperative analgesia in upper abdominal surgery:a randomized,parallel controlled,double-blind,multicenter clinical study[J].Surg Today,2020.doi:10.1007/s00595-019-01951-1
[9] XU Y,TAN Z,CHEN J,et al.Intravenous flurbiprofen axetil accelerates restoration of bowel function after colorectal surgery[J].Can J Anesth,2008,55(7):414
[10] 戴杰,高云睿,梁中卫,等.HPLC法测定氟比洛芬酯注射液的含量和有关物质[J].山东化工,2021,50(20):103
DAI J,GAO YR,LIANG ZW,et al.HPLC simultaneous determination of flurbiprofen axetil and related substance from flurbiprofen axetil injection[J].Shandong Chem,2021,50(20):103
[11] 黄丽,魏龙,李何美,等.58例氟比洛芬不良反应文献分析[J].中国药物警戒,2022,19(4):436
HUANG L,WEI L,LI HM,et al.Literature review of 58 cases of adverse drug reactions induced by flurbiprofen[J].Chin J Pharmacov,2022,19(4):436
[12] 谢菡,陈思煌,陈大宇,等.不同厂家氟比洛芬酯注射液有效性和安全性的真实世界研究[J].医药导报,2023,42(2):193
XIE H,CHEN SH,CHEN DY,et al.Comparison of efficacy and safety between flurbiprofen axetil injections from two manufacturers:a real world study[J].Her Med,2023,42(2):193
[13] YBH15412004-2014Z氟比洛芬酯注射液.国家食品药品监督管理总局药品标准[S].2014
YBH15412004-2014Z Flurbiprofen axetil injection.National Standards of the People’s Republic of China[S].2014
[14] YBH00382018氟比洛芬酯注射液.国家食品药品监督管理总局药品标准[S].2018
YBH00382018 Flurbiprofen Axetil Injection.Standard of China Food and Drug Administration[S].2018
[15] 程栎,郑瑞峥,周丽莹,等.一种氟比洛芬酯药品中有关杂质的检测方法:中国,CN202011080757.8[P].2024-07-28
CHENG L,ZHENG RZ,ZHOU LY,et al.A Detection Method for Impurities in a Flurbiprofen Ester Drug:China,CN202011080757.8[P].2024-07-28
[16] 中华人民共和国药典2020年版.二部[S].2020:913
ChP 2020.Vol Ⅱ[S].2020:913
[17] EP 11.0.Vol ⅡP 11.0.Vol Ⅱ[S]. 2023:2815
[18] 俞伟,尹超,颜国明.氟比洛芬酯的合成进展[J].广东化工,2020,47(6):3
XU W,YIN C,YAN GM.Progress in the synthesis of flurbiprofen[J].Gongdong Chem,2020,47(6):3
