摘要
目的:建立富马酸沃诺拉赞原料药有关物质的HPLC测定方法。方法:采用Symmetry C_(18)色谱柱(4.6 mm×250 mm,5μm),对降解杂质和工艺杂质进行定量分析,以0.02 mol·L^(-1)磷酸氢二钾(加入磷酸调pH至5.0)-乙腈为流动相,梯度洗脱,流速1.0 mL·min^(-1),检测波长为235 nm,柱温30℃。用UPLC-MS鉴定其中1个未知杂质;采用ACQUITY UPLC BEH C_(18)色谱柱(50 mm×2.1 mm,1.7μm),以乙腈为流动相A,0.1%乙酸+2 mmol·L^(-1)醋酸铵溶液为流动相B,梯度洗脱,ESI离子源,正离子扫描方式,检测离子m/z为361.9。结果:主峰与各杂质峰间能达到基线分离,沃诺拉赞及各杂质质量浓度在0.2~2.0μg·m L^(-1)范围内与峰面积呈良好的线性关系(r=0.999),最低检测限为0.1μg·m L^(-1)。3批样品有关物质测定结果显示,已知杂质和未知杂质含量均低于0.1%;其中1个未知杂质为1-[5-(2-氟苯基)-1-(N-氧化物吡啶-3-基-磺酰基)-1H-吡咯-3-基]-N-甲基甲胺。结论:本法可作为富马酸沃诺拉赞质量控制的方法。
Objective：To establish an HPLC method for the determination of the related substances in vonoprazan fumarate.Methods：The test for degradation and process impurities was performed on a symmetry C18 column（4.6 mm×250 mm,5 μm）,the mobile phase consisted of 0.02 mol·L^-1 potassium phosphate solution（adjusted to pH 5.0 with phosphoric acid）-acetonitrile with gradient elution at the flow rate of 1.0 mL·min^-1;the detection wavelength was 235 nm and the column temperature was 30 ℃.One of the unknown impurities was identified by UPLC-MS with the gradient elution.The separation was performed on the ACQUITY UPLC BEH C18 column（50 mm×2.1 mm,1.7 μm）,using acetonitrile as mobile phase A and 0.1% acetic acid＋2 mmol·L^-1 ammonium acetate as the mobile phase B.The mass spectrometer was operated in positive electrospray ionization modeswith the transition m/z of 361.9.Results：The impurity peaks were separated well from the main peak.A good linearity was observed over the range of 0.2-2.0 μg·mL^-1（r=0.999）,the LOD was 0.1 μg·mL-1;the determination results of the three batches of samples showed that each of the impurities was less than 0.1%.The unknown impurity identified was 3-（（2-（2-fluorophenyl）-4-（（methylamino）methyl）-1 H-pyrrol-1-yl）sulfonyl）pyridine-1-oxide.Conclusion：The established determination method can be used for quality control of vonoprazan fumarate.
作者
余倩盈
姚凯
刘育
李建其
周爱南
YU Qian-ying;YAO Kai;LIU Yu;LI Jian-qi;ZHOU Ai-nan(Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 201203, China;Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai 201203, China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2018年第4期728-733,共6页
Chinese Journal of Pharmaceutical Analysis
