Two analytical methods have been developed for the determination of zafirlukast, a novel anti-asthmatic drug: high performance liquid chromatography (HPLC) and derivative spectrophotometry (DS). HPLC with ultraviolet detection at 225 nm is carried out with a Symmetry Shield RP18 column and a mobile phase constituted of acetonitrile and 0.01 M potassium dihydrogen phosphate buffer, adjusted the pH to 3.5 with 0.1 M KOH. The LC method is simple, rapid, selective and stability indicating. Indole was used as internal standard for the purpose of quantification of zafirlukast in HPLC. Spectrophotometry uses the third order derivative of the UV spectrum at 251.1 nm (Δλ value 2.1 nm) for determination. Both methods were fully validated and a comparison was made. The results confirm that the methods are highly suitable for its intended purpose.