HPLC法测定福多司坦原料药及其制剂中有关物质的含量  

Content Determination of the Related Substances in Fudosteine Raw Material and Its Preparations by HPLC

作　　者：郭志渊 赵欣庆 朱恒怡 袁军 GUO Zhiyuan;ZHAO Xinqing;ZHU Hengyi;YUAN Jun(Sichuan Institute for Food and Drug Control,Chengdu 611731,China)

机构地区：[1]四川省食品药品检验检测院

出　　处：《中国药房》2019年第13期1764-1769,共6页China Pharmacy

基　　金：四川省科技计划项目(No.2018SZ0001)

摘　　要：目的:建立福多司坦原料药及其制剂中有关物质含量测定的方法。方法:以国内8家企业生产的福多司坦原料药或制剂为样品。采用高效液相色谱(HPLC)法(外标法)测定杂质A、B、C的含量,色谱柱为MGⅡC18,流动相为0.12%己烷磺酸钠溶液(pH2.0),流速为1.0mL/min,检测波长为210nm,柱温为35℃,进样量为20μL。采用HPLC法(加校正因子的主成分自身对照法)测定杂质E、F、G的含量,色谱柱为Altech Altima C18,流动相为0.05 mol/L磷酸盐缓冲液-乙腈-水(梯度洗脱),流速为0.5mL/min,检测波长为200nm,柱温为30℃,进样量为20μL。结果:杂质A、B、C、E、F、G的检测质量浓度线性范围分别为0.446~22.291、0.202~20.158、0.101~12.082、0.111 0~11.100、0.210 4~10.520、0.221 6~11.080μg/mL,检测限分别为5.57、1.01、1.99、2.22、4.21、4.43ng,定量限分别为11.14、2.02、3.98、4.45、8.42、8.85ng;杂质E、F、G的校正因子分别为0.91、1.42、1.73,相对保留时间分别为0.88、1.95、3.08;精密度(n=6)、稳定性[杂质A(4h,n=3),其余各杂质(24h,n=7)]试验的RSD均小于2.0%,平均加样回收率分别为98.0%、97.3%、102.4%、99.4%、98.9%、96.4%,RSD分别为1.4%、1.5%、1.1%、0.9%、1.2%、0.5%(n=9);8家福多司坦原料药或制剂生产企业中杂质总含量均<1.1%。结论:该方法灵敏度高、专属性好,可用于福多司坦原料药及其制剂中有关物质的定量研究。OBJECTIVE:To establish the method for content determination of the related substance in fudosteine raw material and its preparations.METHODS:Fudosteine or its preparations produced by 8 domestic enterprises were taken as samples.HPLC method(external standard)was used to determine the contents of impurities A,B and C.The separation was performed on MGⅡC18 column with mobile phase consisted of 0.12%sodium hexane sulfonate solution(pH 2.0)at flow rate of 1.0 mL/min.The detection wavelength was set at 210 nm,column temperature was 35℃and sample size was 20μL.The contents of impurities E,F,G were determined by HPLC method(principal component self-contrast method with correction factor).The separation was performed on Altech Altima C18 column with mobile phase consisted of 0.05 mol/L phosphate buffer-acetonitrile-water(gradient elution)at the flow rate of 0.5 mL/min.The detection wavelength was set at 200 nm,and the column temperature was 30℃.The sample size was 20μL.RESULTS:The linear ranges of impurity A,B,C,E,F and G were 0.446-22.291,0.202-20.158,0.101-12.082,0.111 0-11.100,0.210 4-10.520,0.221 6-11.080μg/mL,respectively.The limits of detection were 5.57,1.01,1.99,2.22,4.21,4.43 ng,respectively.The limits of quantitation were 11.14,2.02,3.98,4.45,8.42,8.85 ng,respectively.The relative correction factors of impurities E,F and G were 0.91,1.42 and 1.73,respectively;their relative retention time were 0.88,1.95 and 3.08.RSDs of precision(n=6)and stability[impurity A(4 h,n=3),other impurities(24 h,n=7)]tests were all lower than 2.0%.The average recoveries were 98.0%,97.3%,102.4%,99.4%,98.9%,96.4%,respectively;RSDs were 1.4%,1.5%,1.1%,0.9%,1.2%,0.5%(n=9),respectively.Total contents of substances in fudosteine raw material or its preparation produced by 8 enterprises were all lower than 1.1%.CONCLUSIONS:Established method is sensitive and specific.The method can be used for the quantitative study on related substances in fudosteine raw material and its preparations.

关 键 词：福多司坦 有关物质 高效液相色谱法 含量测定 原料药 

分 类 号：R927.2[医药卫生—药学] O657.72[理学—分析化学]