Identification, characterization and cytotoxicity in vitro assay of nitazoxanide major degradation product.

Stress studies of the broad-spectrum antiparasitic nitazoxanide were conducted in order to isolate and elucidate the major degradation product involved in thermal, acid, alkaline, oxidative and photolytic decomposition of the drug in solution and solid state. The major degradation product was identified and characterized using techniques namely LC-DAD, (1)H NMR, (13)C NMR, IR, and MS/MS. The stability of nitazoxanide raw material and nitazoxanide in tablets and in suspension powder was studied under different conditions and the results suggest the formation of the same deacetylated degradation product occur in all cases. This product was also studied in order to determine the preliminary cytotoxicity in vitro with mononuclear cells. Compared with nitazoxanide, the degradation product showed a higher cytotoxicity at a concentration of 40 μg mL(-1) after 48 h of incubation, under tested conditions. Therefore, stress studies showed that special care must be taken during the preparation, manufacture, and storage of this pharmaceutical drug.