【摘要】 对抗病毒药溴夫定原料药进行影响因素试验的光照降解实验表明,有2个光降解杂质产生。我们用大孔吸附树脂分离纯化分别得到这2个杂质。结合质谱和核磁,我们确定了这2个杂质的分子结构,其中杂质2为溴夫定的顺式异构体,杂质3为溴夫定的二聚体,杂质3属于未曾有文献报道的新化合物。对于其形成历程,我们认为杂质2的生成可能经历了光诱导的顺-反异构化反应历程,杂质3可能是光诱导的[2+2]环加成的反应机理,机理分析进一步推导出了杂质3的优势立体构型。这2个光降解杂质的获得和其分子结构的明确,为溴夫定原料药的分析方法开发和质量研究提供了物质基础,同时也为溴夫定原料药药包材的选择提供了数据支撑,确保溴夫定原料药贮存期间的质量稳定性。更多还原

【Abstract】 To provide reference impurities for drug quality study, two impurities from brivudine(1) were obtained by photoreaction and isolated by means of macroporous absorbent resin. The structures of the impurities were elucidated based on the analysis of MS and NMR. Impurity 2 was a cis-isomer of 1, and impurity 3 was a dimer of 1. According to the mechanism analysis, the spatial configuration of impurity 3 was determination, and the two impurities were produced respectively by photoisomerization of cis-trans and photo-[2+2] cycloaddition reaction. This study provides data support for the selection of API packaging material and ensures the quality stability of 1 during storage.更多还原