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Abstract Background The aim of the present investigation was to improve comprehensive analytical method for the assessment of satranidazole in drug and product with simple, economic, sensitive, and reproducible spectrophotometric method. The drug was analyzed in three different methods by using various solvents where satranidazole (STZ) showed different absorbance maxima (s) and sharp peaks in the first order derivative spectra. Beer’s law range, correlation coefficient, apparent molar absorptivity, etc., were determined for each solvent using all the three methods. Results All the results of analysis were found to be satisfactory which was validated statistically for various parameters and by performing recovery studies in accordance with international conference on harmonization (ICH) guidelines. The developed methods were also compared statistically using one way analysis of variance (ANOVA). Conclusion Three different spectrophotometric methods were developed for satranidazole (STZ) using various inorganic and organic solvents. The analytical methods are found to be simple, sensitive, rapid, specific, and economic, and it can be conveniently employed for the routine analysis, quality control. The sample recoveries from the formulation were in good agreement with its respective label claim.