注射用泮托拉唑钠中有关物质研究  

Study on Related Substances in Pantoprazole Sodium for Injection

作　　者：王晔 刘骅 王辰雯 马莉 WANG Ye;LIU Hua;WANG Chenwen;MA Li(Anhui Food and Drug Control Institute,Hefei,Anhui,China 230051;Hainan Weikang Pharmaceutical Co.,Ltd.,Haikou,Hainan,China 570100)

机构地区：[1]安徽省食品药品检验研究院,安徽合肥230051 [2]海南卫康制药有限公司,海南海口570100

出　　处：《中国药业》2024年第5期63-67,共5页China Pharmaceuticals

基　　金：公共健康社会治理安徽省哲学社会科学重点实验室开放课题[PHG202307]。

摘　　要：目的提高注射用泮托拉唑钠中有关物质的质量标准。方法色谱柱为Thermo Hypersil ODS C18柱(125 mm×4.0 mm,5μm),流动相为0.01 mol/L磷酸二氢钾缓冲液(用20%磷酸调pH至7.0)-[水-乙腈(1∶99,V/V)],梯度洗脱,流速为1.0 mL/min,检测波长为290 nm(杂质A,B,D+F,E)和305 nm(杂质C),柱温为40℃,进样量为20μL。采用加校正因子的主成分自身对照法计算有关物质的含量,杂质A,B,D+F,E按校正因子1.0计算,杂质C按校正因子0.3计算。结果在拟订色谱条件下,出峰顺序依次为杂质C、杂质A、泮托拉唑、杂质D+F、杂质E、杂质B,泮托拉唑与杂质D+F的分离度大于3.0;杂质A、杂质B、杂质C、杂质D+F、杂质E、泮托拉唑的检测限分别为0.24,0.29,0.80,0.71,0.30,0.30 ng。调整流动相梯度洗脱程序后,杂质D和杂质F的分离度大于1.0;检测限均为0.01μg/mL;加样回收率均在90%~110%范围内,RSD低于10.0%(n=9)。6批注射用泮托拉唑钠样品中均检出杂质A(C16H15N3O5F2S)、杂质C(C8H6F2N2OS)、杂质D+F(C17H17F2N3O4S,对映异构体)。结论该方法操作简单、专属性强,可用于注射用泮托拉唑钠中有关物质的质量控制。拟订杂质A、杂质C、其他单个杂质含量均不得过0.2%,杂质B、杂质E含量均不得过0.1%,杂质D、杂质F含量均不得过0.5%,总杂质含量不得过1.0%。Objective To improve the quality standard of related substances in Pantoprazole Sodium for Injection.Methods chromatographic column was Thermo Hypersil ODS C18 column(125 mm×4.0 mm,5μm),the mobile phase was 0.01 mol potassium dihydrogen phosphate buffer(adjusted to pH 7.0 with 20%phosphoric acid)-[water-acetonitrile(1∶99,V/V)]with gradient elution,the flow rate was 1.0 mL/min,the detection wavelength was 290 nm(impurities A,B,D+F,E)and 305 nm(impurity C),the column temperature was 40℃,and the injection volume was 20μL.The content of related substances was calculated using the self-contrast method of principal component with correction factors.Impurities A,B,D+F,and E were calculated with a correction factor of 1.0,while impurity C was calculated with a correction factor of 0.3.Results Under the chromatographic conditions,the peak order was as follows:impurity C,impurity A,pantoprazole,impurity D+F,impurity E,and impurity B.The isolation degree between the pantoprazole peak and the impurity D+F peak was higher than 3.0.The limits of detection(LOD)of impurities A,B,C,D+F,E,and pantoprazole were 0.24,0.29,0.80,0.71,0.30,and 0.30 ng,respectively.After adjusting the gradient elution program of the mobile phase,the isolation degree of impurities D and F was higher than 1.0,and the LOD was 0.01μg/mL.The impurity recovery rates were in the range of 90%-110%with an RSD<10.0%(n=9).Impurity A(C16H15N3O5F2S),impurity C(C8H6F2N2OS),and impurity D+F(C17H17F2N3O4S,enantiomer)were detected in six batches of Pantoprazole Sodium for Injection.Conclusion This method is simple with strong specificity,which can be used for the quality control of related substances in Pantoprazole Sodium for Injection.The content of impurities A,C,and other single impurities shall not exceed 0.2%,the content of impurities B and E shall not exceed 0.1%,the content of impurities D and F shall not exceed 0.5%,and the content of total impurities shall not exceed 1.0%.

关 键 词：注射用泮托拉唑钠 主成分自身对照法 相对校正因子 有关物质 

分 类 号：R917[医药卫生—药物分析学] R975.2[医药卫生—药学]