HPLC法测定5-(2-氟苯基)-1H-吡咯-3-甲腈中的有关物质  

Determination of Related Substances in 5-(2-Fluorophenyl)-1H-Pyrrole-3-Acetonitrile by HPLC

作　　者：张昱 郑忠辉[1] ZHANG Yu;ZHENG Zhonghui(Shandong Xinhua Pharmaceutical Co.,Ltd.,Zibo 255086,China)

机构地区：[1]山东新华制药股份有限公司,山东淄博255086

出　　处：《山东化工》2024年第22期182-186,共5页Shandong Chemical Industry

摘　　要：目的:建立一种测定富马酸伏诺拉生起始物料5-(2-氟苯基)-1H-吡咯-3-甲腈有关物质的分析方法。方法:色谱柱Thermo Acclaim^(TM) polar advantageⅡC_(18)(4.6 mm×250 mm, 5μm),流动相A:乙腈-0.05%磷酸水溶液体积比30∶70,流动相B:纯乙腈,在梯度洗脱条件下,流速为1.0 mL·min^(-1),检测器波长为254 nm,色谱柱柱温为30℃,进样量为10μL。结果:该色谱条件下,各杂质与主成分分离度良好,检测限度较低。杂质1,2,3,4,5,6和杂质7分别在0.124~4.957μg·mL^(-1)(r=0.999 7)、0.124~4.944μg·mL^(-1)(r=0.999 9)、0.110~5.477μg·mL^(-1)(r=0.9999)、0.070~5.625μg·mL^(-1)(r=0.999 9)、0.133~5.305μg·mL^(-1)(r=0.999 9)、0.138~5.511μg·mL^(-1)(r=0.999 9)、0.181~5.172μg·mL^(-1)(r=0.999 9)范围内与峰面积呈现较好线性。结论:该方法按照ICH指南进行全面验证,发现该方法具有良好的特异性、线性、重复性和稳定性,可用于5-(2-氟苯基)-1H-吡咯-3-甲腈的有关物质测定,为其质量控制提供方法保障。Objective:Establishment of a high-performance liquid chromatography method for the determination of related substances in the starting material 5-(2-fluorophenyl)-1H-pyrrole-3-acetonitrile of vonoprazan fumarate.Methods:Thermo Acclaim TM polar advantageⅡC 18 column(4.6 mm×250 mm,5μm)was performed,the mobile phase a was acetonitrile-0.05%phosphoric acid solution(30∶70),and the mobile phase B was acetonitrile.Gradient elution was used,the flow rate was 1.0 mL·min-1,the column temperature was 30℃,the detection wavelength was 254 nm,and the injection volume was 10μL.Results:Under the selected chromatographic conditions,the specificity was fine,the detection limit was low.Impurity 1,2,3,4,5,6 and 7 in the concentration ranges of 0.124~4.957μg·mL^(-1)(r=0.9997),0.12~4.944μg·mL^(-1)(r=0.9999),0.110~5.477μg·mL^(-1)(r=0.9999),0.070~5.625μg·mL^(-1)(r=0.9999),0.133~5.305μg·mL^(-1)(r=0.9999),0.138~5.511μg·mL^(-1)(r=0.9999)and 0.181~5.172μg·mL^(-1)(r=0.9999)revealed good linear relationship with the peak area.Conclusion the performance of this method was validated in accordance to the regulatory guidelines recommended by the international conference on harmonisation(ICH)and this validation included specificity,linearity,repeatability and stability.It can be used to determine the related substances in 5-(2-fluorophenyl)-1H-pyrrole-3-acetonitrile and can provide a method guarantee for its quality control.

关 键 词：富马酸伏诺拉生 5-(2-氟苯基)-1H-吡咯-3-甲腈 有关物质 高效液相色谱法 质量控制 

分 类 号：TQ460[化学工程—制药化工]