ISOLATION AND CHARACTERIZATION OF TWO NOVEL DEGRADANT PRODUCTS IN ITRACONAZOLE BY USING PREP‑HPLC, HRMS AND NMR

To in-line with the ICH guideline Q1A(R2), Itraconazole was subjected to acidic ,basic and oxidative stress . Drug was stable in all the conditions except oxidation stress. Separated the two oxidative degradation products, by using gradient elution, C8 column on preparative HPLC and structural elucidation was performed by using 1D & 2D NMR spectroscopic studies and mass analysis. Those are recognized as 1-(4-((2-((1H-1,2,4-triazol-1-yl)methyl)-2(2,4-dichlorophenyl)-1,3-dioxolan-4-yl) methoxy) phenyl)-4-(4-(1-(sec-butyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol4-yl)phenyl)piperazine 1,4-dioxide(DP-1), 1-(4-((2-((1H-1,2,4-triazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3dioxolan-4-yl)methoxy)phenyl)-4-(4-(1-(sec-butyl)-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)phenyl) piperazine 1oxide (DP-2).These degradents are innovative impurities which are found first time in this product. Moreover, the degradation mechanism from Itraconazole to DP-1 and DP-2 was also proposed.