高效液相色谱法测定创新药物艾托莫德原料药中的有关物质  

Determination of related substances in a new drug aituomode by HPLC

作　　者：李彤[1] 张婷婷[1] 金波[1] 肖琼[1] 汪小涧[1] 尹大力[1] 马辰[1] LI Tong;ZHANG Ting-ting;JIN Bo;XIAO Qiong;WANG Xiao-jian;YIN Da-li;MA Chen(Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]中国医学科学院药物研究所,北京100050

出　　处：《药物分析杂志》2018年第7期1210-1216,共7页Chinese Journal of Pharmaceutical Analysis

基　　金：国家"重大新药创制"科技重大专项资助项目(2012ZX09301002-001)

摘　　要：目的:建立高效液相色谱法测定抗银屑病新药艾托莫德(SYL927)原料药中有关物质的含量。方法:采用HC-C_8色谱柱(4.6 mm×250 mm,5μm),以乙腈-0.2%醋酸钠缓冲液为流动相进行梯度洗脱,流速1.0 m L·min^(-1),柱温40℃,检测波长283 nm,进样量20μL。对SYL927与合成工艺中的6种中间体和3种副产物的分离分析方法进行了验证。结果:SYL927与9种有关物质可完全分离,分离度大于1.5。所有的有关物质在线性范围内线性关系良好,r均大于0.999 9;检测下限均在0.5~2 ng范围,定量下限均在1~4 ng范围;平均回收率(n=7)在100.2%~101.4%,RSD均≤2.2%。3批样品的总杂质含量≤1.0%。结论:该方法适用于艾托莫德原料药有关物质的控制和稳定性考察。Objective：To establish an HPLC method for the determination of related substances in a new anti-psoriasis drug aituomode（SYL927）bulk drug.Methods：Separation was performed on an HC-C_8 chromatography column（4.6 mm×250mm,5μm）,and the detection wavelength was 283 nm.The mobile phase was acetonitrile-0.2%sodium acetate buffer solution,with gradient elution at a flow rate of 1.0 m L·min^（-1）.The column temperature was 40℃and the injection volume was20μL.The method was validated for the determination of the related substances in aituomode bulk drugs,including 6 kinds of intermediates and 3 kinds of by-products.Results：SYL927 and all the related substances were well separated,with the resolution greater than 1.5.All of the analytes was good linear relationships（r0.999 9）in the linear range.The detection limits were 0.5-2 ng,and the quantification limits were 1-4 ng,respectively.The average recoveries（n=7）were between 100.2%and 101.4%,with the RSD≤2.2%.The total content of related substances in each of the three batches of aituomode samples was less than 1.0%.Conclusion：The method was suitable for the quality control and stability test of aituomode bulk drug.

关 键 词：艾托莫德(SYL927) 抗银屑病新药 有关物质检测 方法学验证 高效液相色谱法 

分 类 号：R917[医药卫生—药物分析学]