RESUMO
Four impurities in fluconazole API sample obtained from a recently proposed synthetic process were detected by HPLC. One of the impurities was unknown having not been reported previously. This less polar unknown impurity was isolated from the crude sample of fluconazole bulk drug using semi-preparative HPLC. Structure of impurity was elucidated as 2-(2-(dimethylamino)-4-fluorophenyl)-1,3-di(3H-1,2,4-triazol-1-yl)propan-2-ol by using NMR spectroscopy(1H, 13C, 19F, 1H-1H, 1H-13C, HMBC and nOe) and mass spectrometry. The formation and synthesis of the impurity was discussed.
Assuntos
Antifúngicos/isolamento & purificação , Contaminação de Medicamentos/prevenção & controle , Fluconazol/isolamento & purificação , Antifúngicos/química , Cromatografia Líquida de Alta Pressão , Fluconazol/química , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
Three impurities were detected in the LC/MS analysis of fluconazole bulk drug substance. Two of the impurities were unknowns having not been reported previously. Structural assignment of these impurities was carried out by LC/MS/MS using electrospray ionization source and an ion trap mass analyzer. Structural elucidation using nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy was facilitated by newly developed rapid preparative isolation method. These impurities were characterized as 1-(1-H-1,2,4-triazole-1-yl) propane-2,3-diol and Z-2-(2,4-difluorophenyl)-3-(1-H-1,2,4-triazole-1-yl)-2-propen-1-ol. Their formation and synthesis are discussed.
