A new, Simple, sensitive and accurate spectrophotometric methods have been developed for the determination of sulfanilamide (SNA) drug in pure and in synthetic sample. This method based on the reaction of sulfanilamide (SNA) with 1,2-napthoquinone-4-sulphonic acid (NQS) to form N-alkylamono naphthoquinone by replacement of the sulphonate  group of the naphthoquinone sulphonic acid by an amino group. The colored chromogen shows absorption maximum at 455 nm. The optimum conditions of condensation reaction forms were investigated by: (1) univariable method, by optimizing the effect of experimental variables; (different bases, reagent concentration, borax concentration and reaction time),     (2) central  composite design (CCD) including the effect of three experimental factors (reagent concentration, borax concentration, and reaction time). The linearity ranges of sulfanilamide are (5-30 µg.mL -1 ) at 455 nm with molar absorptivity (6.9568×10 4 - 7.0774×10 4 L.mol -1 .cm -1 ), Sandell's sensitivity index (2.4753 - 2.4330 μg.cm -2 ) and detection limit of (0.546 – 0.536 µg.mL -1 ) for each procedure respectively. The results showed there are no interferences of excipients on the determination of the drug. The proposed method has been successfully applied for the determination of sulfanilamide in pure and in synthetic sample. Keywords: Spectrophotometric determination, Sulfanilamide, Central  composite design, 1, 2-napthoquinone-4-sulphonic acid (NQS).