Radiochemical stability of fluconazole in the solid state.

The effect of ionizing radiation in doses between 20 and 200 kGy on physicochemical properties of fluconazole (alpha-(2,4-diflurophenyl)-alpha-(1H-triazol-1-methyl)-1H-1,2,4-triazole-1-ethanol) in the solid state was examined. A number of qualitative and quantitative methods such as scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), ultraviolet (UV) and infrared (IR) spectroscopy, thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC) and organoleptic analysis were used to determine and analyse any changes resulting from irradiation. A change in colour from white to cream was observed at even smallest dose (20 kGy) and as the dose increased the colour deepened from salmon pink to orange at the highest dose of 200 kGy. The UV method showed an increase in absorbance at lambda(max) and an appearance of an additional band in the range 280-310 nm for irradiated samples. These changes were associated with the appearance of one to two decomposition products observed by TLC. Depending on the dose of radiation, the HPLC method detected between 2 and 3 radiolysis products and the decreasing fluconazole content from 0.48 to 7.12%. The remaining analytical methods (SEM, IR and NMR) did not provide any conclusive information in respect of radiological stability of fluconazole. The results indicate that fluconazole is a compound of low radiological stability and should not be sterilized using gamma, beta or E-beam radiation.