HPLC法测定硝苯地平原料药有关物质  

Determination of related substances in nifedipine by HPLC

作　　者：李成文 刘静 马浩 刘秀朋 王文波 LI Cheng-wen;LIU Jing;MA Hao;LIU Xiu-peng;WANG Wen-bo(Dezhou Deyao Pharmacy Co.,Ltd.,Dezhou 253019,China)

机构地区：[1]德州德药制药有限公司,德州253019

出　　处：《药物分析杂志》2024年第12期2095-2104,共10页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立高效液相色谱法测定硝苯地平原料药的有关物质。方法:采用PFP(250 mm×4.6 mm,5μm)色谱柱,以20 mmol·L^(-1)磷酸二氢钾和甲醇为流动相进行梯度洗脱,流速1.0 mL·min^(-1),柱温30℃,检测波长265 nm。结果:硝苯地平以及杂质D、邻硝基苯甲醛、单酰胺、内酯、杂质C、去氢-N-氧化物、杂质A、杂质B、对硝苯地平和间硝苯地平10个已知杂质色谱峰之间的分离度良好,已知杂质间分离度均≥1.5,硝苯地平前后杂质峰与主峰分离度均≥2.0。以上各杂质的质量浓度在0.0002~0.015 mg·mL^(-1)范围内线性关系良好(r>0.999,n=7),相关系数分别为1.000、1.000、1.000、1.000、0.9999、0.9999、0.9999、1.000、0.9999、0.9999,平均回收率(n=9)分别为93.1%(RSD=2.3%)、110.6%(RSD=1.9%)、109.2%(RSD=2.0%)、111.0%(RSD=2.1%)、108.1%(RSD=1.9%)、112.4%(RSD=1.8%)、110.8%(RSD=1.9%)、91.5%(RSD=3.1%)、98.9%(RSD=2.7%)、110.1%(RSD=2.6%),检测限为0.00006 mg·mL^(-1),定量限为0.0002 mg·mL^(-1)。3批硝苯地平原料药样品测定结果显示,已知杂质及其他最大单个杂质的含量均<0.1%,杂质总含量<0.5%。结论:经方法学验证,本方法灵敏度高,专属性好,可用于硝苯地平原料药有关物质测定。Objective:To establish an HPLC method for the determination of related substances in nifedipine.Methods:HPLC was adopted on a PFP column(250 mm×4.6 mm,5μm)with a gradient elution system of 20 mmol·L^(-1)potassium dihydrogen phosphate solution and methanol,the flow rate was 1.0 mL·min^(-1),and the column temperature was maintained at 30℃.The detection wavelength was set at 265 nm.Results:The resolutions were good between the peaks of nifedipine and ten known impurities,including impurity D,2-nitrobenzaldehyde,monoamide,hydroxy dehydro lactone,impurity C,dehydro-N-oxide,impurity A,impurity B,m-nifedipine,p-nifedi-pine.The resolutions between the known impurity peaks were not less than 1.5,the resolutions between the main peak of nifedipine and it's front and back impurity peaks were not less than 2.0.The calibration curves of mass concentration of above known impurities were linear respectively in their concentration range of 0.0002-0.015 mg·mL^(-1)(r>0.999,n=7).The correlation coefficients of above known impurities were1.000,1.000,1.000,1.000,0.9999,0.9999,0.9999,1.000,0.9999,0.9999,respectively.The average recovery rates of above known impurities were 93.1%(RSD=2.3%),110.6%(RSD=1.9%),109.2%(RSD=2.0%),111.0%(RSD=2.1%),108.1%(RSD=1.9%),112.4%(RSD=1.8%),110.8%(RSD=1.9%),91.5%(RSD=3.1%),98.9%(RSD=2.7%),110.1%(RSD=2.6%),respectively.The detection limit of above known impurities was 0.00006 mg·mL^(-1),the quantification limit of above known impurities was 0.0002 mg·mL^(-1).The impurity determination results of the three batches of nifedipine samples showed that the content of the known impurities and the maximum single unknown impurity were less than 0.1%,the total impurities contents were less than 0.5%.Conclusion:The method has good sensitivity and specificity,and it is suitable for the quality control of nifedipine.

关 键 词：硝苯地平 有关物质 工艺杂质 降解杂质 质量控制 高效液相色谱 梯度洗脱 抗高血压药物 

分 类 号：R917[医药卫生—药物分析学]