阿普唑仑杂质的合成
Synthesis of the Impurities of Alprazolam
余增辉 1王辉 1黄思瑜 1杨相平 1许向阳1
作者信息
- 1. 江苏恩华药业股份有限公司,江苏徐州 221116;江苏省中枢神经药物研究重点实验室,江苏徐州 221116
- 折叠
摘要
制备了阿普唑仑(1)的3个杂质(杂质D、H和J),虽在EP 10.0版中收录,但合成路线为首次报道.另外,在1原料药的稳定性研究中,发现并制备了新的杂质Q,通过高分辨质谱和核磁共振光谱确定其为[5-氯-2-[3-[[[(7-氯-5-羟基-5-苯基-4,5-二氢-[1,2,4]三唑[4,3-a]唑啉-1-基)甲基]氨基]甲基]-5-甲基-4H-1,2,4-三唑-4-基]苯基](苯基)甲酮.合成上述4个杂质,对1原料药和制剂的质量研究具有重要意义.
Abstract
This study prepared three impurities of alprazolam(1)namely impurities D,H,and J,which were recorded in the EP 10.0,but their synthetic routes had not been reported in the literature.Additionally,during the stability study of 1 bulk drug,a new impurity Q was discovered.Its chemical structure was determined as[5-chloro-2-[3-[[[(7-chloro-5-hydroxy-5-phenyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1-yl)methyl]amino]methyl]-5-methyl-4H-1,2,4-triazol-4-yl]phenyl](phenyl)methanone through high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy.The successful preparation of these four impurities is of great significance for the quality research of 1 bulk drug and its formulations.
关键词
阿普唑仑/有关物质/合成Key words
alprazolam/related substance/synthesis引用本文复制引用
出版年
2024
NETL
NSTL
万方数据