反相离子对色谱法测定双氯芬酸二乙胺中的杂质  

Determination of impurities in diclofenac diethylamine raw material by reversed phase ion pair chromatography

作　　者：何汇洋 李瑞瑞 高磊 马志宁 张鹏[1] HE Huiyang;LI Ruirui;GAO Lei;MA Zhining;ZHANG Peng(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2020年第10期918-926,共9页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立一种同时测定双氯芬酸二乙胺原料药中10种杂质的反相离子对色谱法。方法采用Inertsil ODS-SP(250 mm×4.6 mm,5μm)色谱柱,以体积分数0.25%的四甲基氢氧化铵水溶液(以磷酸溶液调节pH值至6.5)-甲醇-乙腈为流动相,梯度洗脱,流速为1.0 mL·min^-1,柱温为25℃,检测波长为280 nm。结果空白溶剂及主成分双氯芬酸二乙胺对已知/未知杂质的检测均无干扰,杂质A在质量浓度0.496 0~2.976 mg·L^-1内,杂质B、C、E、5、3′-羟基双氯芬酸、4′-羟基双氯芬酸、2,6-二氯苯酚、双氯芬酸二聚体、2,6-二氯联苯胺在质量浓度0.250 0~1.500 mg·L-1内线性关系良好。各已知杂质的平均回收率分别为99.97%、98.76%、99.50%、99.45%、98.77%、98.88%、99.83%、98.63%、100.0%和99.04%。采用该方法对3批双氯芬酸二乙胺原料药进行有关物质检查,检测到的各已知/未知单杂及总杂质含量均符合各质量标准要求。结论方法学验证结果表明该方法符合杂质分析要求,适用于双氯芬酸二乙胺原料药的有关物质检查。Objective To establish a method for the simultaneous determination of the 10 impurities of diclofenac diethylamine raw material by reversed phase ion pair chromatography.Methods The determination was achieved on a Inertsil ODS-SP column(250 mm×4.6 mm,5 μm) with a gradient elution system of 0.25% tetramethylammonium hydroxide solution(adjusting pH to 6.5 with phosphate acid)-methanol-acetonitrile.The flow rate was 1.0 mL·min-1 with detection wavelength of 280 nm,column temperature was maintained at 25 ℃.Results The blank solvent and the main component diclofenac diethylamine had no interference on the detection of known/unknown impurities.The impurity A showed good relationship in the range of 0.4960-2.976 μg·mL^-1.Impurity B,C,E,5,3′-hydroxydiclofenac,4′-hydroxydiclofenac,2,6-dichlorophenol,diclofenac dimer impurity,2,6-dichlorobenzidine showed a good linearity in the range of 0.2500-1.500 μg·mL^-1.And the average recoveries were 99.97%,98.76%,99.50%,99.45%,98.77%,98.88%,99.83%,98.63%,100.0%,99.04%,respectively.Three batches of diclofenac diethylamine were inspected,and the known/unknown single and total impurity contents met the requirements of various quality standards.Conclusion The method validation results proved that it had good specificity,sensitivity and accuracy,and met the requirements of impurity analysis of diclofenac diethylamine raw material.

关 键 词：双氯芬酸二乙胺 杂质 反相离子对色谱法 

分 类 号：R917[医药卫生—药物分析学]