Determination of 4-( 4-Amino-3-fluorophenoxy )-N-methylpyridine-2-carboxamide in Regorafenib by LC-MS/MS
- VernacularTitle:LC-MS/MS法测定瑞戈非尼中4-(4-氨基-3-氟苯氧基)-N-甲基吡啶-2-甲酰胺
- Author:
Xiuzhen WANG
;
Zhiyun ZHANG
;
Haixia YANG
;
Guomin ZHAO
;
Shide WU
- Keywords:
Regorafenib;
Genotoxic impurity;
4-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide;
LC-MS/MS
- From:
China Pharmacist
2017;20(2):348-350
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To establish an LC-MS/MS method for the determination of 4-( 4-amino-3-fluorophenoxy )-N-methylpyri-dine-2-carboxamide ( AFP-PMA) as a genotoxic impurity in regorafenib. Methods: The content of AFP-PMA was determined by an LC-MS/MS method. A Waters XBridge Shield RP18 column was adopted to separate the samples and the column temperature was 50℃. The mobile phase consisted of 5 mmol·L-1ammonium 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. 9998) 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 0.000241% 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 genotoxic impurity AFP-PMA in regorafenib.
