LC-ESI-MSMS表征瑞戈非尼的强制降解产物  

Characterization of the Force-degraded Products of Regorafenib by LC-ESI-MSMS

作　　者：郭莉君 董梅 王嘉林 郭莉红 

机构地区：[1]渭南市食品药品检验所,陕西渭南714000 [2]洛阳市食品药品检验所 [3]渭南市疾病预防控制中心

出　　处：《中国药师》2018年第9期1594-1597,1610,共5页China Pharmacist

摘　　要：目的:采用LC-ESI-MSMS对瑞戈非尼原料药中的杂质进行表征。方法:对瑞戈非尼原料药HPLC色谱系统进行优化,液相色谱条件为ACE Aq C_(18)色谱柱(250 mm×4.6 mm,5μm),以乙腈-0.1%磷酸水为流动相,梯度洗脱,流速为1.0 ml·min^(-1),检测波长为254 nm,柱温为30℃。液质联用色谱条件为BEH C_(18)(100 mm×2.1 mm,1.7μm)色谱柱,流动相A为25mmol·L^(-1)甲酸溶液,流动相B为乙腈,梯度洗脱,流速为0.3 ml·min^(-1),电喷雾电离源(ESI),扫描模式为全扫(SCAN)与碰撞诱导解离(CID),正离子模式,离子源温度300℃,气体流速12 L·min^(-1),毛细管电压:0.8 k V。结果:瑞戈非尼强制降解杂质分离良好,通过一级质谱与二级质谱碎片离子推测出瑞戈非尼5个强制降解产物的结构。结论:LC-ESI-MSMS能够作为瑞戈非尼强制降解产物的结构推测的有力工具,为瑞戈非尼质量研究提供支持。Objective： To characterize the force-degraded products of regorafenib by LC-ESI-MSMS. Methods： The HPLC method for the determination of regorafenib API was optimized. An ACE Aq C18 （250 mm × 4.6 mm,5 μm） column was used, the mobile phase was acetonitrile and 0.1% phosphoric acid with gradient elution, the flow rate was 1.0 ml·min - l, the column temperature was 30℃, and the detection wavelength was 254 nm. The parameters of mass spectrometry were as follows： a BEH C18 （ 100 mm × 2.1 mm, 1.7 μm） column was used, the mobile phase A was 25 mmol · L-1 formic acid, the mobile phase B was acetonitrile, the flow rate was 0.3 ml · min - 1 with gradient elution, electro spray ionization was applied with full scan in CID positive mode, the interface tempera- ture was 300℃ ,the gas flow rate was 12 L · min-l , and the capillary voltage was 0.8 kV. Results： The force-degraded impurities of regorafenib were well separated, and 5 impurities of regorafenib were predicted from MS1 and MS2 fragments. Conclusion： LC-ESI- MSMS can be used as a powerful tool for the structure prediction of the force-degraded products of regorafenib, which is helpful for the quality research of regorafenib.

关 键 词：瑞戈非尼 液相色谱-电喷雾-串联质谱 强制降解 有关物质 

分 类 号：R917[医药卫生—药物分析学]