超临界流体色谱法测定盐酸厄洛替尼原料药及片剂中的有关物质  

Determination of the Related Substances in Erlotinib Hydrochloride Bulk Drug and Tablets by Supercritical Fluid Chromatography

作　　者：金薇 张少敏 乐健 杨永健 JIN Wei;HANG Shaomin;LE Jian;YANG Yongjian(Shanghai Institute for Food and Drug Control,Shanghai 201203;NMPA Key Lab.for Quality Analysis of Chemical Drug Preparations,Shanghai 201203;School of Pharmacy,Fudan University,Shanghai 201203)

机构地区：[1]上海市食品药品检验研究院,上海201203 [2]国家药品监督管理局化学药品制剂质量分析重点实验室,上海201203 [3]复旦大学药学院,上海201203

出　　处：《中国医药工业杂志》2024年第1期89-95,共7页Chinese Journal of Pharmaceuticals

基　　金：上海市科委资助项目(22142201800)。

摘　　要：采用超临界流体色谱(SFC)系统分离并测定盐酸厄洛替尼(1)及其4种有关物质。采用Torus 2-PIC柱(3.0 mm×100 mm,1.7μm),以超临界二氧化碳-甲醇为流动相进行梯度洗脱,进样量为1μL,柱温为50℃,流速为1.0 mL/min。结果显示,各化合物在7 min内出峰并分离完全;4种有关物质分别在0.5~40、2~60、0.4~40、0.5~40μg/mL内,1在5~100μg/mL内,线性关系良好。1、杂质A、杂质B、杂质C和杂质D的LOD分别为0.2、0.2、0.5、0.1、0.2μg/mL;LOQ分别为0.5、0.5、2.0、0.4、0.5μg/mL。各有关物质的加样回收率(n=3)在96.0%~104.2%,RSD均小于3.0%。建立的方法快速有效、灵敏度高、绿色环保,可有效用于1原料药及片剂的质量控制。A supercritical fluid chromatography(SFC)method was established for the separation and determination of erlotinib hydrochloride(1)and its four related substances.A Torus 2-PIC column(3.0 mm×100 mm,1.7μm)was used with the mobile phase containing a mixture of supercritical CO2 and methanol by gradient elution.The injection volume was 1μL,the column temperature was 50℃,and the flow rate was 1.0 mL/min.The results showed that each compound peaked and was completely separated within 7 minutes.And it was linear for four related substances and 1 in the ranges of 0.5-40,2-60,0.4-40,0.5-40,5-100μg/mL,respectively.The LODs of1 and impurities A,B,C,D were 0.2,0.2,0.5,0.1,0.2μg/mL,respectively,and the LOQs were 0.5,0.5,2.0,0.4,0.5μg/mL,respectively.The recoveries(n=3)of four related substances were between 96.0%and 104.2%,with RSDs all less than 3.0%.The established method is rapid,effective,highly sensitive,environmentally friendly,which can be effectively used for quality control of 1 bulk drug and tablets.

关 键 词：盐酸厄洛替尼 原料药 片剂 有关物质 超临界流体色谱 

分 类 号：R917[医药卫生—药物分析学]