Three sensitive and reproducible spectrophotometric methods are developed for the determination of sulfasalazine (H2SS) in pure and in pharmaceutical preparations. The first two methods are based on the complexation reaction of H2SS as bidentate (O-O) hard Lewis base with complexing agent Fe(III) or Mn(II) hard Lewis acid. The third method is based on the oxidation of H2SS drug with alkaline KMnO4 to produce green manganate species. These reactions were monitored spectrophotometrically at maximum absorbance's 495, 460 and 610 nm for Fe(III), Mn(II) and KMnO4 respectively. Variables affecting these reactions were carefully studied and the conditions were optimized. The stoichiometry of each reaction was also determined. The
equilibrium, stability constants (K, β) and the free energy changes (ΔG◦) of complexes formation were calculated. Under optimized experimental conditions, Beer's law is obeyed in the concentration range 7.96-39.80, 19.92-79.61 and 1.99-11.94 μgml-1 for Fe(III), Mn(II) and KMnO4 reagents respectively. The apparent molar absorptivity, Sandell sensitivity, detection and quantification limits are also calculated. These methods are successfully applied for the determination of H2SS in commercially pharmaceutical formulations. Statistical comparison of the results are in good agreement with the reported methods.