基于HPLC-Q-TOF-MS的非那雄胺原料杂质结构及来源分析

Analysis of Structure and Source of Impurity in Finasteride Raw Materials Based on HPLC-Q-TOF-MS

为优化非那雄胺(Finasteride)杂质控制和生产工艺,本研究采用高效液相色谱-四极杆飞行时间质谱法(High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry,HPLC-Q-TOF-MS)分析非那雄胺原料中的主要杂质结构,并结合强制降解试验推测部分杂质的来源。本研究共分离出15种杂质,并初步推测了杂质1,2,5,6,8,10,13,14等8种杂质的结构,其他7种杂质因含量过低或受其他因素干扰,未推断出其结构。强制降解试验结果表明,杂质1,3,5,7,9,10,11,12,14,15为工艺杂质,杂质2,4,6,8和C可能是降解杂质,也可能是工艺杂质。非那雄胺生产企业应优化生产工艺,并在贮藏及运输过程中控制温度,减少非那雄胺降解反应的发生。

In order to optimize the impurity control and production process of Finasteride,this study used High Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry(HPLC-Q-TOF-MS)to analyze the main impurity structure in finasteride raw materials,and combined with forced degradation test to speculate the source of some impurities.In this study,a total of 15 impurities were isolated,and the structures of 8 impurities,such as 1,2,5,6,8,10,13,14,were preliminarily speculated.The structures of the other 7 impurities were not inferred because of their low content or interference by other factors.The results of forced degradation test show that impurities 1,3,5,7,9,10,11,12,14 and 15 are process impurities,and impurities 2,4,6,8 and C may be degradation impurities or process impurities.Finasteride manufacturers should optimize the production process,and control the temperature during storage and transportation to reduce the occurrence of finasteride degradation reaction.