昂拉地韦潜在基因毒性杂质的合成、表征和检测
Synthesis,Characterization and Detection of Potential Genotoxic Impurity of Onradivir
李波 1刘呈武 1刘卓伟 1黎志豪1
作者信息
- 1. 广东众生睿创生物科技有限公司工艺开发部,广东广州 510700
- 折叠
摘要
为了对流感Ⅰ类新药昂拉地韦的潜在基因毒性杂质进行研究,合成了昂拉地韦原料药中潜在基因毒性杂质3-叠氮基-5-氟-1-(四氢-2H-吡喃-2-基)-1H-吡唑并[3,4-b]吡啶(SMI-H),其结构通过核磁共振氢谱、碳谱、质谱进行表征.采用自行开发并验证的液相色谱-质谱法(LC-MS)对昂拉地韦原料药和关键起始物料3-溴-5-氟-1-(四氢-2H-吡喃-2-基)-1H-吡唑并[3,4-b]吡啶(SMI)进行杂质的检测.结果表明:在昂拉地韦中未检出该杂质,而在SMI中有检出(0.1％～0.2％),但杂质含量低于标准限度(≤0.3％),因此昂拉地韦的安全风险是可控的.
Abstract
This article aims to study the potential genotoxic impurities of the new class I influenza drug,Onradivir.3-Azide-5-fluoro-1-(tetrahydro-2H-pyrano-2-yl)-1H-pyrazole[3,4-b]pyridine(SMI-H),which is a potentially genotoxic impurity in the Onradivir,was synthesized with 2-chloro-5-fluoronicotinonitrile as the starting material.The structure of the target compound was identified by 1H NMR,13C NMR and MS(ESI).The content detection was established by LC-MS method and the results showed that it was not detected in the Onradivir,but in the SMI(0.1％～0.2％).The impurity content was lower than the standard limitation(≤0.3％).So the safety risk was controllable in the Onradivir.
关键词
昂拉地韦/SMI-H/流感/合成/结构表征/基因毒性Key words
onradivir/SMI-H/influenza/synthesis/structural characterization/genotoxic impurity引用本文复制引用
出版年
2024
NETL
NSTL
维普
万方数据