盐酸甲氧氯普胺注射液中有关物质检测方法研究  

Study on the Determination of Related Substances in Metoclopramide Dihydrochloride Injections

作　　者：陈露 耿雪 林秋婕 陈赞民 蔡姗英 聂黎行[2] CHEN Lu;GENG Xue;LIN Qiujie;CHEN Zanmin;CAI Shanying;NIE Lixing(Department of Drug Control,Hainan Inspection and Testing Research Institute,Haikou 570216,China;National Institute for Food and Drug Control,Beijing 102629,China)

机构地区：[1]海南省检验检测研究院药品检验所,海口570216 [2]中国食品药品检定研究院,北京102629

出　　处：《药学与临床研究》2024年第5期407-411,共5页Pharmaceutical and Clinical Research

摘　　要：目的:建立高效液相色谱-加校正因子的主成分自身对照法测定盐酸甲氧氯普胺注射液中的有关物质,为该产品的质量控制和评价提供数据支持。方法:采用赛分Sepax Amethyst C_(18)-H色谱柱(4.6 mm×250 mm,5μm),流动相A为0.02 mol·L^(-1)磷酸溶液(加三乙胺调pH至3.8),流动相B为乙腈,梯度洗脱,流速1.0 mL·min^(-1),柱温35℃,检测波长275 nm,进样量为20μL。结果:主成分峰与各杂质色谱峰分离良好,甲氧氯普胺及各杂质在各自质量浓度范围内与峰面积呈良好线性关系(r=1.0000,n=6),检测限在0.03~0.05μg·mL^(-1),定量限在0.10~0.16μg·mL^(-1),杂质1~5的校正因子分别0.71、0.79、1.10、0.96和0.67;平均回收率为98.7%~100.6%(n=9),重复性、精密度和稳定性均符合相关要求。2家企业6批次的盐酸甲氧氯普胺注射液采用加校正因子的主成分自身对照法测定的结果与对照品外标法基本一致。与国内外药典方法比较,本方法对单杂质、总杂质和特定杂质均进行了控制,且分离效能、检出的杂质个数和杂质量均高于其他药典方法。结论:建立的高效液相色谱-加校正因子的主成分自身对照法可用于盐酸甲氧氯普胺注射液的有关物质测定,为其有关物质质量控制方法的改进提供了数据支持。Objective:To establish an HPLC-main component self-contrast method with correction factors for the determination of related substances in metoclopramide dihydrochloride injections,so as to provide data support for their quality control and evaluation.Methods:The separation was performed on a Sepax Amethyst C_(18)-H column(4.6 mm×250 mm,5μm).Mobile phase A was 0.02 mol·L^(-1) phosphoric acid solution(adjust to pH 3.8 with triethylamine),mobile phase B was acetonitrile.The flow rate was 1.0 mL·min^(-1) with gradient elution.The detection wavelength was 275 nm,the column temperature was 35℃,and the injection volume was 20μL.Results:Metoclopramide and the impurities were separated well.The linear relationship between peak area and concentration at respective ranges of metoclopramide and 5 known impurities were good enough(r=1.0000,n=6).The limits of quantitation were 0.10-0.16μg·mL^(-1) and the limits of detection were 0.03-0.05μg·mL^(-1).The average recoveries of impurities 1-5 were 98.7%-100.6%(n=9)and the correction factors of impurities 1-5 were 0.71,0.79,1.10,0.96 and 0.67,respectively.The repeatability,precision and stability met the requirements.The results of 6 batches metoclopramide dihydrochloride injections from 2 different companies obtained by using a main component self-contrast method with correction factors were basically consistent with those obtained by a reference substance method.Compared with the domestic and foreign pharmacopoeia methods,this method had more comprehensive control for single impurities,total impurities and specific impurities.The separation efficiency and identified number of impurities were higher and more than the other pharmacopoeia methods.Conclusion:The established HPLC-main component self-contrast method with correction factors can be used for the determination of related substances in metoclopramide dihydrochloride injections,and provide data support for the improvement of its quality control method.

关 键 词：盐酸甲氧氯普胺注射液 有关物质 高效液相色谱法 校正因子 主成分自身对照法 质量控制 

分 类 号：R917[医药卫生—药物分析学]