摘要
目的定向合成磷酸奥司他韦干混悬剂稳定性研究过程中产生的未知杂质,以提高对磷酸奥司他韦干混悬剂的质量控制。方法以磷酸奥司他韦为原料,分别与葡萄糖、葡萄糖降解物5-羟甲基糠醛及柠檬酸反应生成杂质AB及C1、C2,通过HPLC按加校正因子主成分外标法以峰面积计算杂质含量。结果与结论4个杂质结构均经^(1)H-NMR、^(13)C-NMR和MS谱确证,其中磷酸奥司他韦干混悬剂在高温和加速条件下杂质A、C1和C2含量增加明显,并超过鉴定限,故可将杂质A、C1和C2作为已知杂质订入质量标准控制,按特定单杂控制,限度分别为0.5%、0.2%和0.2%。
In order to improve the quality control of oseltamivir phosphate dry suspension,four unknown impurities,which generated during the stability study of oseltamivir phosphate dry suspension,were synthesized.Oseltamivir phosphate,as the raw material,was reacted with glucose,glucose-degrading compound 5-hydroxymethylfurfural and citric acid to generate impurities A,B,C1 and C2.The impurity contents were calculated by the HPLC peak areas according to the external standard method of principal component plus correction factor.The structures of four impurities were confirmed by^(1)H-NMR,^(13)C-NMR and MS.Impurities A,C1 and C2 increased significantly under high temperature and acceleration conditions,exceeding the identification limit.So impurities A,C1 and C2 were included in the quality standard control as known impurities,which were controlled according to specific single impurities,with limits of 0.5%,0.2%and 0.2%,respectively.
作者
陈佳佳
朱丽娟
周志慧
钟健
CHEN Jia-jia;ZHU Li-juan;ZHOU Zhi-hui;ZHONG Jian(The Second People's Hospital of Huai'an,Huai'an 223001,China;Jiangsu ChiataiQingjiang Pharmaceutical Co.,Ltd.,Huai'an 223001,China)
出处
《中国药物化学杂志》
CAS
2023年第6期440-445,共6页
Chinese Journal of Medicinal Chemistry
关键词
磷酸奥司他韦
降解杂质
未知杂质
oseltamivir phosphate
degradable impurities
unknown impurity
