UPLC-Q-TOF-MS研究依拉地平原料药的降解杂质  

Study on the degradation impurities of Isradipine by UPLC-Q-TOF-MS

作　　者：杨长花[1] 王月茹[1] 刘峰[1] 彭修娟[1] YANG Changhua;WANG Yueru;LIU Feng;PENG Xiujuan(Shaanxi Institute of International Trade & Commerce,Xianyang,Shaanxi,712046 P.R.China)

机构地区：[1]陕西国际商贸学院

出　　处：《华西药学杂志》2019年第3期286-290,共5页West China Journal of Pharmaceutical Sciences

基　　金：生物医药创新制药技术研究院士专家工作站项目(陕科协发[2017]事企字15号)

摘　　要：目的系统分析国产依拉地平原料药降解杂质谱的构成,通过对比国外药典,确定其原料药中杂质的降解路线、种类及限度。方法采用强制降解(光照、强酸碱及氧化)得到依拉地平原料药的降解杂质色谱峰,通过制备液相色谱纯化及高分辨率飞行时间质谱(UPLC-Q-TOF-MS)解析,并结合原料药合成路线对降解杂质结构及来源进行分析。结果明确了6个杂质的结构及类型,对比国外药典中质量标准杂质控制限度及国际人用药品注册技术要求国际协调会(ICH)相关指导原则,明确了国产依拉地平原料药的主要控制降解杂质种类。结论按照9.0版《欧洲药典》中色谱条件检测国产依拉地平原料中的相对保留时间为0.63、0.85的杂质是其主要降解杂质,对原料药的质量影响最明显。OBJECTIVE To carry out systematic analysis of the composition of the degradation impurities of domestically produced Isradipine API,and to determine the degradation route,type and limit of the impurity by referring to foreign Pharmacopoeia.METHOD In this study,UPLC-Q-TOF-MS was used to systematically analyze the composition of the impurity profile of Isradipine.Forced degradation testing(In excess of light conditions,high and low pH,oxidation)was carried out.RESULTS The structure of six impurities were clarified.The quality control standard of impurity in foreign pharmacopoeia and ICH related guidelines were compared,and the main controlled degradation impurities of domestic Isradipine API were clarified.CONCLUSION Impurities with a relative retention time of 0.63 and 0.85 according to the chromatographic conditions of EP 9.0 can be thought as the main degradation impurities of Isradipine,and should be controlled in Isradipine quality standard.

关 键 词：依拉地平 原料药 强制降解实验 制备液相 高分辨质谱 飞行时间质谱 降解杂质 国际人用药品注册技术要求国际协调会指导原则 

分 类 号：R917[医药卫生—药物分析学]