摘要
建立了厄贝沙坦制剂中9种N-亚硝胺基因毒性杂质的气相色谱串联三重四极杆质谱(GC-MS/MS)检测方法。采用VF-WAXms毛细管色谱柱(0.25 mm×30 m×0.5μm)对系列N-亚硝胺化合物进行分离。结果显示9种N-亚硝胺化合物在所测浓度范围内线性关系良好,定量限为0.3~78.3 ng/ml,检测限为0.1~20.6 ng/ml。平均加样回收率为81.43%~123.2%,RSD≤7.80%(n=3)。将所建方法应用于检测厄贝沙坦制剂,检出N-亚硝基二乙胺、N-亚硝基吗啉和N-亚硝基二苯胺。N-亚硝基二乙胺检出范围为0.11~0.54μg/g,N-亚硝基吗啉检出范围为0.16~0.17μg/g,N-亚硝基二苯胺检出范围为0.11~1.95μg/g。所建方法灵敏度高、准确度好,可同时测定厄贝沙坦制剂中9种N-亚硝胺杂质,为其质量控制提供参考。
A GC-MS/MS method was established for the determination of nine genotoxic N-nitrosamine impurities in irbesartan preparations.The separation of a series of N-nitrosamines was performed on a VF-WAXms capillary column(0.25 mm×30 m×0.5μm).The results showed that nine N-nitrosamines were linear in the test concentration ranges.The quantification limits of nine N-nitrosamines were 0.3-78.3 ng/ml and the detection limits were 0.1-20.6 ng/ml.The average recoveries of nine N-nitrosamines were between 81.43%and 123.2%,with RSDs(n=3)no more than 7.80%.The proposed method was applied to investigate different irbesartan preparations,and N-nitrosodiethylamine was detected in the range of 0.11-0.54 mg/g,N-nitrosomorpholine was detected in the range of 0.16-0.17 mg/g,N-nitrosodiphenylamine was detected in the range of 0.11-1.95μg/g.This method has good sensitivity and high accuracy,and it is suitable for the simultaneous determination of nine N-nitrosamines in irbesartan preparations,which provides a reliable method for the quality control of the drug.
作者
葛雨琦
叶晓霞
乐健
杨永健
王彦
GE Yuqi;YE Xiaoxia;LE Jian;YANG Yongjian;WANG Yan(School of Pharmacy,Fudan University,Shanghai 201203;Shanghai Institute for Food and Drug Control,Shanghai 201203;Key Lab.for Quality Analysis of Chemical Drug Preparations,National Medical Products Administration,Shanghai 201203)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2020年第6期759-764,共6页
Chinese Journal of Pharmaceuticals
基金
国家药典委员会综改课题——基因毒性杂质通用检测方法的建立(ZG2018-4-03)
上海市市场监督管理局2020年度科技项目计划——药品中基因毒性杂质质量控制研究(2019-53)。
