摘要
目的:建立抗癌新药瑞戈非尼中遗传毒性杂质4-(4-氨基-3-氟苯氧基)-N-甲基吡啶-2-甲酰胺(AFP-PMA)的含量测定方法。方法:采用LC-MS/MS法测定;利用Waters XBridge Shield RP_(18)色谱柱(150 mm×3.0 mm,3.5μm)进行分离,以5mmol·L^(-1)乙酸铵溶液(A)-乙腈(B)为流动相,采用梯度洗脱(0~9 min,5%B→90%B),流速为1.0 ml·min^(-1),柱温50℃;ESI离子源,正离子扫描方式,多反应监测(MRM)模式扫描,检测离子通道为m/z 262.2→244.1。结果:AFP-PMA浓度在2.41~980.90 ng·ml^(-1)范围内与峰面积呈良好线性关系(r=0.999 8);定量限为8.02 ng·ml^(-1);检出限为2.41 ng·ml^(-1),约为供试品溶液浓度的0.000 241%;平均加样回收率为100.95%,RSD为2.37%(n=9)。结论:本方法专属性强、灵敏度高、准确度好,可用于瑞戈非尼中4-(4-氨基-3-氟苯氧基)-N-甲基吡啶-2-甲酰胺的含量测定。
Objective： To establish an LC-MS/MS method for the determination of 4-（4-amino-3-fluorophenoxy）-N-methylpyri- dine-2-earboxamide （AFP-PMA） as a genotoxie impurity in regorafenib. Methods： The content of AFP-PMA was determined by an LC-MS/MS method. A Waters XBridge Shield RPxscolumn was adopted to separate the samples and the column temperature was 50 ℃. The mobile phase consisted of 5 mmol L-1 ammonium acetate aqueous （A）-acetonitrile （B） with gradient elution （0 -9 min, 5% B →90% B） at a flow rate of 1.0 ml min-1. An electrospray ionization source （ESI） was used in a positive-ion and multiple reactions monitoring mode. The ion channel was m/z 262.2→244.1. Results： The standard curve was linear within the range of 2.41-980.90 ng ml- 1 （ r = 0. 999 8） and the limit of quantification was 8.02 ng ml- 1. The limit of detection was 2.41 ng ml - 1, which was e- quivalent to 0. 000 241% for the concentration of regorafenib. The average recovery was 100.95% and RSD was 2.37% （n = 9 ）. Conclusion： The method has good specificity, promising accuracy and high sensitivity, which can be used for determining the trace genotoxie impurity AFP-PMA in regorafenib.
作者
王秀珍
张治云
杨海霞
赵国敏
吴世德
Wang Xiuzhen Zhang Zhiyun Yang Haixia Zhao Guomin Wu Shide(Shandong Provincial Key Laboratory of Chemical Drugs, Shandong Academy of Pharmaceutical Seienee, Ji＇nan 250101, China Shandong Provincial Engineering Research Center for Transmueosal and Transdermal Drug Delivery, Shandong Freda Pharmaeeutieal Group Co. Ltd. Shandong Provincial Engineer- ing Research Center for Medicines of Orthopedic Pain, Shangdong Mingren Freda Pharmaceutical Co. Ltd.)
出处
《中国药师》
CAS
2017年第2期348-350,共3页
China Pharmacist
基金
"重大新药创制"科技重大专项(编号:2009ZX09301-013)
