摘要
目的:建立超高效液相色谱法测定富马酸伏诺拉生有关物质的方法。方法:采用ZORBAX SB-C_(18)色谱柱(4.6 mm×150 mm,1.8μm),流动相A为0.025 mol·L^(-1)磷酸盐缓冲溶液(pH 6.0)-甲醇-乙腈(14∶5∶1),流动相B为0.025 mol·L^(-1)磷酸盐缓冲溶液(pH 6.0)-乙腈(3∶7),采用梯度洗脱,流速1.0 mL·min^(-1),柱温30℃,检测波长230 nm,进样量20μL。结果:杂质A、杂质C、杂质D、杂质F、杂质G、杂质H、杂质J、杂质K、杂质L、杂质M、杂质N和伏诺拉生分别在0.04177~2.088μg·mL^(-1)(r=1.0000)、0.07479~3.740μg·mL^(-1)(r=1.0000)、0.07335~3.668μg·mL^(-1)(r=1.0000)、0.1000~2.004μg·mL^(-1)(r=1.0000)、0.1325~6.623μg·mL^(-1)(r=1.0000)、0.09300~1.860μg·mL^(-1)(r=1.0000)、0.1380~2.7530μg·mL^(-1)(r=1.0000)、0.1350~2.698μg·mL^(-1)(r=1.0000)、0.1130~2.257μg·mL^(-1)(r=1.0000)、0.05060~2.530μg·mL^(-1)(r=0.9999)、0.1420~2.846μg·mL^(-1)(r=1.0000)、0.1190~2.382μg·mL^(-1)(r=0.9998)浓度范围内与峰面积呈良好线性关系。上述各杂质的平均回收率(n=9)分别为97.24%、102.12%、99.46%、98.29%、101.51%、100.84%、99.18%、101.20%、98.49%、103.63%、96.49%。采用该检测方法对5批样品进行有关物质检测,其中杂质C、杂质M、杂质N检出量均≤0.05%,杂质H、其他最大单个杂质检出量均≤0.10%,总杂质检出量均≤0.31%。结论:经方法学验证,本法专属性强、灵敏度高、准确度高,可用于富马酸伏诺拉生原料的有关物质测定,为其质量控制提供方法保证。
Objective:To establish a method for the determination of related substances in vonoprazan fumarate by ultra high performance liquid chromatography(UPLC).Methods:ZORBAX SB-C_(18) column(4.6 mm×150 mm,1.8μm)was performed,the mobile phase A was 0.025 mol·L^(-1) phosphate buffer solution(pH 6.0)-methanol-acetonitrile(14∶5∶1),and the mobile phase B was 0.025 mol·L^(-1) phosphate buff er solution(pH 6.0)-acetonitrile(3∶7).Gradient elution was used,the fl ow rate was 1.0 mL·min^(-1),the column temperature was 30℃,the detection wavelength was 230 nm,and the injection volume was 20μL.Results:Impurity A,impurity C,impurity D,impurity F,impurity G,impurity H,impurity J,impurity K,impurity L,impurity M,impurity N and vonoprazan in the concentration ranges of 0.04177-2.088μg·mL^(-1)(r=1.0000),0.07479-3.740μg·mL^(-1)(r=1.0000),0.07335-3.668μg·mL^(-1)(r=1.0000),0.1000-2.004μg·mL^(-1)(r=1.0000),0.1325-6.623μg·mL^(-1)(r=1.0000),0.09300-1.860μg·mL^(-1)(r=1.0000),0.1380-2.7530μg·mL^(-1)(r=1.0000),0.1350-2.698μg·mL^(-1)(r=1.0000),0.1130-2.257μg·mL^(-1)(r=1.0000),0.05060-2.530μg·mL^(-1)(r=0.9999),0.1420-2.846μg·mL^(-1)(r=1.0000),and 0.1190-2.382μg·mL^(-1)(r=0.9998)revealed good linear relationship with the peak area.The rates of recovery(n=9)of the above impurities were 97.24%,102.12%,99.46%,98.29%,101.51%,100.84%,99.18%,101.20%,98.49%,103.63%,and 96.49%,respectively.Five batches of samples were tested for related substances by this detection method,in which the detection amount of impurity C,impurity m and impurity N was<0.05%,the detection amount of impurity h and other largest single impurities was≤0.10%,and the total detection amount of impurities was≤0.31%.Conclusion:The method has been proved to be exclusive,sensitive and accurate.It can be used to determine the related substances in vonoprazan fumarate materials and can provide a method guarantee for its quality control.
作者
赵静芝
宿亮
朱婧
朱跃芳
吴超男
Zhao Jingzhi;Su Liang;Zhu Jing;Zhu Yuefang;Wu Chaonan(Zhuzhou Qianjin Pharmaceutical Co.,Ltd.,Zhuzhou 412000,China;Zhuzhou Institute for Food and Drug Control,Zhuzhou 412000,China)
出处
《中国药事》
CAS
2022年第7期800-809,共10页
Chinese Pharmaceutical Affairs
基金
湖南省自然科学基金资助项目(编号2017JJ2123)。
关键词
消化性溃疡
富马酸伏诺拉生
有关物质
超高效液相色谱法
质量控制
peptic ulcer
vonoprazan fumarate
related substances
ultra high performance liquid chromatography
quality control
