HPLC法测定氯雷他定原料药的有关物质  

Determination of related substances in loratadine by HPLC

作　　者：刘晶晶 韦小怡 江坤 刘敏 李玉兰 王铁杰 LIU Jing-jing;WEI Xiao-yi;JING Kun;LIU Min;LI Yu-lan;WANG Tie-jie(Shenzhen Institute for Drug Control,Shenzhen Key Laboratory of Drug Quality Standard Research,NMPA Key Laboratory for Bioequivalence Research of Generic Drug Evaluation,Shenzhen 518057,China)

机构地区：[1]深圳市药品检验研究院深圳市药品质量标准研究重点实验室、国家药品监督管理局仿制药评价生物等效性研究重点实验室,深圳518057

出　　处：《药物分析杂志》2023年第6期1036-1043,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：2016年国家药典委员会药品标准提高课题(307)。

摘　　要：目的:建立HPLC法同时测定氯雷他定原料药中9个有关物质(杂质A~I)。方法:采用YMC-Triart C_(18)(250 mm×4.6 mm,5μm)色谱柱,以庚烷磺酸钠缓冲液-乙腈为流动相,梯度洗脱,流速1.0 mL·min^(-1),柱温40℃,检测波长254 nm,进样体积20μL。结果:对照品氯雷他定与9个已知杂质A~I的色谱峰均能良好分离,对照品氯雷他定及杂质A~I分别在0.215~10.712μg·mL^(-1)(r=0.9999)、0.544~10.930μg·mL^(-1)(r=0.9999)、0.202~10.108μg·mL^(-1)(r=1.000)、0.202~10.141μg·mL^(-1)(r=1.000)、0.198~9.923μg·mL-1(r=1.000)、0.580~11.625μg·mL^(-1)(r=1.000)、0.489~9.783μg·mL^(-1)(r=0.9999)、0.223~11.249μg·mL^(-1)(r=1.000)、0.197~9.874μg·mL^(-1)(r=0.9999)、0.199~9.971μg·mL^(-1)(r=1.000)浓度范围内线性关系良好(n=6);对照品氯雷他定及杂质A~I的定量限分别为0.078、0.302、0.146、0.102、0.075、0.251、0.242、0.088、0.196、0.127μg·mL^(-1);杂质A~I的平均回收率(n=9)分别为98.1%、100.0%、97.4%、100.2%、98.3%、102.1%、102.0%、100.0%、97.3%;4个厂家氯雷他定原料药测定结果显示,1个厂家的样品中杂质F的含量较高,应引起重视。结论:该方法灵敏度高,专属性强,可区分不同厂家氯雷他定原料药的质量,可用于氯雷他定原料药的有关物质检查。Objective:To establish an HPLC method for simultaneous determination of 9 related substances including impurity A-I in loratadine.Methods:The determination was performed on a YMC-Triart C_(18)column(250 mm×4.6 mm,5μm).The mobile phase consisted of sodium heptanesulfonate buffer solution and acetonitrile with gradient elution.The flow rate was 1.0 mL·min^(-1),the column temperature was maintained at 40℃,the detection wavelength was set at 254 nm,and the injection volume was 20μL.Results:The resolutions between the peaks of reference substance loratadine and nine known impurities(including impurities A-I)were good.The calibration curves of reference substance loratadine and impurities A-I were linear in their respective weight ranges of 0.215-10.712μg·mL^(-1)(r=0.9999),0.544-10.930μg·mL^(-1)(r=0.9999),0.202-10.108μg·mL^(-1)(r=1.000),0.202-10.141μg·mL^(-1)(r=1.000),0.198-9.923μg·mL^(-1)(r=1.000),0.580-11.625μg·mL^(-1)(r=1.0000),0.489-9.783μg·mL^(-1)(r=0.9999),0.223-11.249μg·mL^(-1)(r=1.000),0.197-9.874μg·mL^(-1)(r=0.9999)and 0.199-9.971μg·mL^(-1)(r=1.000).The limits of quantitation were 0.078,0.302,0.146,0.102,0.075,0.251,0.242,0.088,0.196 and 0.127μg·mL^(-1).The recoveries(n=9)of impurities A-I were 98.1%,100.0%,97.4%,100.2%,98.3%,102.1%,102.0%,100.0% and 97.3%,respectively.The determination results of the four manufactures samples showed that the content of impurity F of one manufacture was high,which worthed attention.Conclusion:This method is sensitive and specific,which can distinguish the quality of loratadine from different manufacturers,and can be used for the determination of related substances in loratadine API.

关 键 词：氯雷他定 抗过敏药 有关物质 相对校正因子 质量控制 高效液相色谱法 

分 类 号：R917[医药卫生—药物分析学]