高效液相色谱法测定盐酸多奈哌齐原料药中的有关物质  

Determination of related substances in donepezil hydrochloride drug substance by HPLC

作　　者：戈东阳 富薪竹 赵旻[1] 张雨萌 王淼[1] 赵春杰[1] GE Dongyang;FU Xinzhu;ZHAO Min(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Jiangsu Hansoh Pharmaceutical Group Co.,Ltd.,Lianyungang 222000,China)

机构地区：[1]沈阳药科大学药学院,沈阳111016 [2]江苏豪森药业集团有限公司,江苏连云港222000

出　　处：《中国处方药》2025年第6期48-52,共5页Journal of China Prescription Drug

摘　　要：目的建立并验证高效液相色谱法(HPLC)用于盐酸多奈哌齐原料药有关物质的检测。方法采用Phenomenex Luna C_(18)(2)色谱柱(4.6 mm×250 mm,5μm),流动相A为0.1%磷酸溶液(使用三乙胺调节pH至6.6),流动相B为乙腈,进行梯度洗脱,流速为1.5 ml/min,柱温为50℃,检测波长为286 nm。结果在该色谱条件下,盐酸多奈哌齐和各种杂质能够有效分离,分离度大于1.5;在酸、碱、光照、氧化及高温条件下各种杂质与降解产物均能良好分离;盐酸多奈哌齐及各种杂质的检测限为0.025~0.1μg/ml,定量限为0.05~0.2μg/ml,线性相关系数(r)>0.9990,加样回收率为98.37%~106.62%,精密度相对标准偏差(RSD)<6%;微调pH值、柱温、流速及更换不同批次色谱柱对系统适用性溶液进行考察,结果表明参数的变化对结果几乎无影响;对照品溶液及系统适用性溶液在室温条件下48 h内稳定。结论所建立的方法可用于盐酸多奈哌齐原料药有关物质测定。Objective To develop and validate a High-Performance Liquid Chromatography(HPLC)method for determination of related substances in drug substance donepezil hydrochloride.Methods Using Phenomenex Luna C_(18)(2)column(4.6 mm×250 mm,5μm).Mobile phase A was 0.1%phosphoric acid solution(pH value was adjusted to 6.6 by triethylamine).Mobile phase B was acetonitrile;gradient elution was performed at a flow rate of 1.5 ml/min.Column temperature was 50℃and detection wavelength was 286 nm.Results Under these chromatographic conditions,all related substances and donepezil hydrochloride could be completely separated(resolution>1.5).Under the conditions of acid,alkali,light,oxidation and high temperature,each impurity and degradation product could be well separated.Donepezil hydrochloride and each impurity’s limit of detection(LOD)was 0.025-0.1μg/ml.limit of quantitation(LOQ)was 0.05-0.2μg/ml,the linear correlation coefficient(r)was more than 0.9990.The recovery rate was 98.37%-106.62%,and the relative standard deviation(RSD)of precision was less than 6%;pH,column temperature,flow rate and batches of column were changed to investigate the system suitability solution.Results showed that the changes on parameters had no effect.Reference solution and system suitability solution were stable within 48 hours at room temperature.Conclusion This established method can be used for the determination of related substances in donepezil hydrochloride drug substance.

关 键 词：盐酸多奈哌齐 高效液相色谱法 有关物质 

分 类 号：R28[医药卫生—中药学]