Implementation of green chemistry to develop HPLC/UV and HPTLC methods for the quality control of Fluconazole in presence of two official impurities in drug substance and pharmaceutical formulations

Abstract

Two eco-friendly chromatographic methods were developed for analysis of Fluconazole (FLU) in presence of its official impurities B and C in drug substance and pharmaceutical formulations. For the HPTLC- densitometry, the separation was achieved using silica gel plates and mobile system consisting of ethyl acetate: water: acetic acid (8: 1: 1 v/v/v). The HPLC/UV was conducted on column C18 and a mixture of (water: ethanol) in gradient elution at flow rate 1.5 mL/min. The developed methods were validated according to ICH guidelines and they were able to determine FLU without interference from its two structurally related impurities with an accepted resolution and at low concentration level. The linearity was achieved over the range 50–500 μg/spot for HPTLC and 1-500 μg/mL for HPLC/UV. The LOD and LOQ values were 41.3 and 50 μg/spot for HPTLC and 0.052 and 0.15 μg/mL for HPLC/UV, respectively. The results were statistically compared to those obtained by reported methods showing no significant difference in terms of accuracy and precision. The green character of the developed methods was assessed and compared with reported methods using four different tools; NEMI, analytical eco-scale, GAPI and AGREE. The developed methods were found to be greener than the reported methods.