HPLC法测定马来酸氨氯地平原料药有关物质  

Determination of related substances in amlodipine maleate raw material by HPLC

作　　者：韩遵圣 吴松 李天磊 刘博 张洁 张驰 HAN Zunsheng;WU Song;LI Tianlei;LIU Bo;ZHANG Jie;ZHANG Chi(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]中国医学科学院&北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《沈阳药科大学学报》2021年第10期1040-1045,共6页Journal of Shenyang Pharmaceutical University

基　　金：“重大新药创制”科技重大专项(2017ZX09101001-005);中国医学科学院医学与健康科技创新工程重大协同创新项目(2017-I2M-1-011)。

摘　　要：目的建立马来酸氨氯地平原料中有关物质的HPLC测定方法。方法采用Waters SunFire C18(250 mm×4.6 mm,5μm)色谱柱;以甲醇乙腈体积分数0.7%三乙胺溶液(取三乙胺7.0 mL,加水稀释至1000 mL,用磷酸调节pH值至3.0±0.1)(V∶V∶V=35∶15∶50)为流动相,流速1.0 mL·min^(-1),柱温30℃;检测波长237 nm。结果氨氯地平与各已知杂质及强降解产物均分离度良好,杂质Ⅰ、Ⅱ、Ⅲ、Ⅳ的质量浓度分别在0.29~9.51 mg·L^(-1)(r=1.000),0.29~9.51 mg·L^(-1)(r=0.9999),0.30~9.51 mg·L^(-1)(r=0.9995)和0.29~9.51 mg·L^(-1)(r=0.9999)范围内与峰面积呈良好的线性关系,校正因子分别为2.65、1.38、1.00、1.34;检测限分别为1.01、4.02、0.49、0.50 ng,定量限分别为4.03、10.01、1.46、1.98 ng。杂质I、杂质Ⅱ、杂质Ⅲ及杂质Ⅳ的回收率(n=9)依次为98.94%、101.63%、101.67%、101.79%,RSD依次为1.45%、1.87%、1.41%、1.43%。3批马来酸氨氯地平样品中已知杂质及未知杂质均小于0.1%,杂质总量均小于0.6%。结论该方法可用于马来酸氨氯地平原料药中有关物质的检测。Objective To establish an HPLC method for the determination of related substances in amlodipine maleate raw material.Methods HPLC was adopted on a C18 column(250 mm×4.6 mm,5μm)with a mobile phase consisting of a mixture of methanol-acetonitrile-0.7%triethylamine solution(7.0 mL of triethylamine was dissolved in 1000 mL of water,and pH was adjusted to 3.0±0.1 with phosphoric acid)(V∶V∶V=35∶15∶50).The flow rate was 1.0 mL·min^(-1).The column temperature was maintained at 30℃and the detective wavelength was 237 nm.Results Amlodipine maleate was well separated from the specified impurities and the forced degradation products.There was a good linearity separately over the ranges 0.29-9.51 mg·L^(-1)(r=1.000)of impurityⅠ,0.29-9.51 mg·L^(-1)(r=0.9999)of impurityⅡ,0.30-9.51 mg·L^(-1)(r=0.9995)of impurityⅢ,and 0.29-9.51 mg·L^(-1)(r=0.9999)of impurityⅣ.The correction factors of 4 impurities were 2.65,1.38,1.00 and 1.34;the limits of detection were 1.01,4.02,0.49 and 0.50 ng,respectively;the limits of quantitation were 4.03,10.01,1.46,1.98 ng,respectively;the recovery rates were 98.94%,101.63%,101.67%and 101.79%,respectively;RSDs were 1.45%,1.87%,1.41%and 1.43%(n=9).The results of related substances in three batches of samples showed that the contents of specified impurities and unknown impurities were less than 0.1%,total impurities were less than 0.6%.Conclusion This method has good specificity and high sensitivity,and can be used for the determination of related substances in amlodipine maleate raw material.

关 键 词：马来酸氨氯地平 有关物质 反相高效液相色谱法 质量控制 

分 类 号：R917[医药卫生—药物分析学]