HPLC法检测依折麦布中的有关物质  

Determination of related substances of ezetimibe by HPLC

作　　者：张大业[1] 王艳丽 王军 ZHANG Da-ye;WANG Yan-li;WANG Jun(Tianjin Chest Hospital,Tianjin 300222,China;Beijing Kangda Pharmaceutical Co.,Ltd.,Beijing 102600,China;Tianjin Wuxi App Tec Co.,Ltd.,Tianjin 300070,China)

机构地区：[1]天津市胸科医院,天津300222 [2]北京康达制药有限公司,北京102600 [3]天津药明康德新药开发有限公司,天津300070

出　　处：《药物分析杂志》2023年第4期620-629,共10页Chinese Journal of Pharmaceutical Analysis

基　　金：天津市科技计划项目(No.18YFZCSY00015)。

摘　　要：目的:建立采用高效液相色谱法测定依折麦布有关物质。方法:采用Agilent TC-C18(250 mm×4.6 mm,5.0μm)色谱柱,以0.05 mol·L^(-1)磷酸二氢钾溶液-乙腈-四氢呋喃(60∶20∶20)为流动相,流速1.0 mL·min^(-1),柱温35℃,检测波长232 nm,进样体积20μL。结果:依折麦布峰与各杂质峰分离良好;依折麦布峰与杂质A、杂质B、杂质C、杂质D、杂质E与杂质F的线性范围分别为0.409~4.090μg·mL^(-1)(r=0.9950)、0.402~4.020μg·mL^(-1)(r=0.9981)、0.408~4.080μg·mL^(-1)(r=0.9991)、0.411~4.110μg·mL^(-1)(r=0.9993)、0.4050~4.050μg·mL^(-1)(r=0.9981)、0.541~5.41μg·mL^(-1)(r=0.9985)、0.657~6.57μg·mL^(-1)(r=0.9975);检测限分别为0.130、0.135、0.135、0.140、0.140、0.180、0.210μg·mL^(-1),定量限分别为0.409、0.402、0.408、0.411、0.405、0.541、0.657μg·mL^(-1);杂质A、杂质B、杂质C、杂质D、杂质E与杂质F的平均回收率分别为99.4%、101.2%、100.1%、101.7%、100.0%、101.0%,RSD分别为0.85%、1.1%、1.0%、0.62%、0.87%、0.72%。3批依折麦布样品检测结果显示,已知杂质及其他最大单个杂质含量均<0.10%,杂质总含量<0.50%。结论:建立的高效液相色谱法方法可靠、准确,可用于依折麦布有关物质的测定。Objective:To develop a method for related substances determination of ezetimibe by HPLC.Methods:Agilent TC-C_(18)column(250 mm×4.6 mm,5.0μm)was used.The mobile phase consisted of 0.05 mol·L^(-1)potassium dihydrogen phosphate solution-acetonitrile-tetrahydrofuran(60∶20∶20)with a flow rate of 1.0 mL·min^(-1).The column temperature was 35℃,the detection wavelength was 232 nm,and the injection volume was 20μL.Results:Chromatographic peaks of ezetimibe and impurities were separated.Linear ranges of ezetimibe,and impurities A,B,C,D,E and F were 0.409-4.090μg·mL^(-1)(r=0.9950),0.402-4.020μg·mL^(-1)(r=0.9981),0.408-4.080μg·mL^(-1)(r=0.9991),0.411-4.110μg·mL^(-1)(r=0.9993),0.4050-4.050μg·mL^(-1)(r=0.9981),0.541-5.41μg·mL^(-1)(r=0.9985),0.657-6.57μg·mL^(-1)(r=0.9975),respectively;LODs were 0.130,0.135,0.135,0.140,0.140,0.180,0.210μg·mL^(-1);LOQs were 0.409,0.402,0.408,0.411,0.405,0.541,0.657μg·mL^(-1).Average recoveries of impurities A,B,C,D,E and F were 99.4%,101.2%,100.1%,101.7%,100.0%,101.0%,and RSDs were 0.85%,1.1%,1.0%,0.62%,0.87%,0.72%.The detection results of 3 batches of ezetimibe samples showed that the contents of known impurities and other maximum single impurity were less than 0.10%,and the total content of impurities was all less than 0.50%.Conclusion:The method is accurate and reliable for determination of related substances of ezetimibe.

关 键 词：高效液相色谱法 依折麦布 原料药 有关物质 工艺杂质 降解杂质 

分 类 号：R917[医药卫生—药物分析学]