富马酸伏诺拉生原料药中残留溶剂的测定

Determination of Residual Solvents in Vonoprazan Fumarate

目的:建立了气相顶空色谱法测定富马酸伏诺拉生原料药中的残留溶剂。方法:色谱柱为以聚乙二醇为键合相的毛细管柱(DB-WAX,30 m×0.32 mm×0.5μm);载气:氮气;柱流速:1.0 mL/min;程序升温:初始温度为40℃,保持2 min,然后以5℃/min的速率升温至70℃,保持2 min,再以30℃/min的速率升温至230℃保持3 min。FID检测器温度:280℃;进样口温度:200℃;顶空瓶平衡温度:100℃;平衡时间为20 min;分流比:25∶1;结果:在该色谱条件下,各残留溶剂峰分离度良好且空白溶剂无干扰峰,四氢呋喃、乙酸乙酯、甲醇、二氯甲烷、乙腈在10%~120%浓度范围内线性关系良好。检测限质量浓度依次为:0.18,0.3,0.6,0.87,0.65μg/mL;定量限质量浓度依次为:0.53,0.99,1.5,2.89,2.18μg/mL;各溶剂精密度和回收率良好。结论:本方法灵敏度和准确度符合要求,便于操作,适用于富马酸伏诺拉生原料药中残留溶剂的测定。

Objective:Headspace gas chromatography was established to determinate the residual solvents of vonoprazan fumarate.Methods:The stationary phase of capillary column(DB-WAX,30 m×0.32 mm×0.5μm)was polyethylene glycol with carrier gas was nitrogen and the column flow rate was 1.0 mL/min.The temperature was programmed at 40℃maintained for 2 min,at a rate of 5℃/min to 70℃for 2 min,and at a rate of 30℃/min to 230℃maintained for 3 min.FID detector temperature:280℃;inlet temperature:200℃;balance temperature of headspace bottle:100℃,balance time:20 min;shunt ratio:25∶1.Results:Under the selected chromatographic conditions,the blank has no interference and the resolution of each residual solvent peak is good.Tetrahydrofuran,ethyl acetate,methanol,dichloromethane and acetonitrile had a good linear relationship within the concentration range of 10%to 120%,respectively.The LOD were 0.18,0.3,0.6,0.87,0.65μg/mL,respectively.The LOQ were 0.53,0.99,1.5,2.89,2.18μg/mL,respectively.All solvents have good precision and recovery.Conclusion:The method is sensitive,accurate and easy to operate.It is suitable for the determination of the residual solvents of vonoprazan fumarate.