米格来宁片有关物质和含量测定方法研究  

Determination of related substances and the contents of migliening tablets

作　　者：宋军 李青翠 孙晋鹏 刘建祯 郭峰兵 SONG Jun;LI Qingcui;SUN Jinpeng;LIU Jianzhen;GUO Fengbing(Shanxi Institute for Food and Drug Control,Taiyuan 030031,China)

机构地区：[1]山西省食品药品检验所,太原030031

出　　处：《中国药品标准》2023年第2期174-181,共8页Drug Standards of China

摘　　要：目的:建立米格来宁片有关物质与含量测定的HPLC方法。方法:采用Thermo AcclaimTM120 C18柱(4.6 mm×250 mm, 5μm)色谱柱;有关物质流动相:以0.01 mol·L^(-1)醋酸钠溶液-乙腈进行梯度洗脱;含量测定流动相为0.01 mol·L^(-1)醋酸钠溶液-乙腈(85∶15);流速1.0 mL·min^(-1);检测波长275 nm;进样量10μL。结果:安替比林和咖啡因分别与11种杂质完全分离,分离度大于1.5,测定杂质F校正因子为1.01,采用高分辨液质联用仪和ADMET Predictor软件推断主要未知杂质结构与毒性;含量测定咖啡因在11.0~109.6μg·mL^(-1)浓度范围内线性关系良好(r=1.000 0),平均回收率为99.03%(n=9),定量限为4.4 ng;安替比林在109.96~1 099.6μg·mL^(-1)浓度范围内线性关系良好(r=1.000 0),平均回收率为100.56%(n=9),定量限为11.0 ng。测定3个药厂9批产品结果均符合规定。结论:本方可用于测定米格来宁片中有关物质(杂质F≤0.03%,总杂质≤0.05%)以及安替比林和咖啡因的含量(安替比林:98.8%~101.4%,咖啡因:84.4%~107.5%)。Objective:To establish a method for the determination of related substances and contents in Migliening Tablets by HPLC.Methods:Thermo Acclaim TM 120 C 18 column(4.6 mm×250 mm,5μm)was used for chromatographic column.The mobile phase of related substances was gradient elution with 0.01 mol·min^(-1) sodium acetate solution-acetonitrile(85∶15).The flow rate was 1.0 ml·min^(-1).The detection wavelength was 275 nm.The injection volume was 10μL.Results:Antipyrine and caffeine were completely separated from 11 impurities,the separation degree was greater than 1.5,and the calibration factor of impurity F was 1.01,the structure and toxicity of main unknown impurities were inferred by high resolution liquid chromatography-mass spectrometry and ADMET Predictor software,and the linear relationship of caffeine was good in the range of 11.0-109.6μg·mL^(-1)(r=1.0000),with an average recovery of 99.03%(n=9),in the range of 109.96-1099.6μg·mL^(-1) in antipyrine,the linear relationship was good(r=1.0000),the average recovery was 100.56%(n=9),and the quantitative limit was 11.0 ng.The test results of 9 batches of products from 3 pharmaceutical factories were in accordance with the regulations.Conclusion:The method can be used for the determination of related substances(impurities F≤0.03%,total impurities≤0.05%)and the contents of antipyrine and caffeine(antipyrine:98.8%-101.4%,caffeine:84.4%-107.5%).

关 键 词：米格来宁片 有关物质 安替比林 咖啡因 含量测定 高效液相色谱法 

分 类 号：R921.2[医药卫生—药学]