There are more than 100000 different species of fungi, many of which are beneficial to food and fermentation industries; however, hundreds are pathogenic to plants and a few hundreds have been shown to cause infection in humans. 1)Treatment of fungal infections is considerably more difficult than that of a bacterial infection as many fungal infections occur in poorly vascularised or avascular tissues. 2)Ketoconazole (KT), clotrimazole (CL), miconazole nitrate (MN) and econazole nitrate (EN) (Fig. 1) are imidazole derivatives which represent a large and emerging group of synthetic antifungal agents.Several methods for the determination of ketoconazole, clotrimazole, miconazole nitrate and econazole nitrate, have been described in the literature. They include volumetric, 3) spectrophotometric, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] spectrofluorimetric methods, [19][20][21] capillary electrophoresis method, 22,23) thin layer chromatography, 24,25) gas chromatography 26,27) and high performance liquid chromatographic methods. [28][29][30][31][32][33][34][35][36][37][38][39][40] However, the imidazole antifungal derivatives are susceptible for the degradation due to the effect of temperature, oxygen, light and pH and the degraded products may be pharmacologically inactive. In addition, there are many antifungal pharmaceutical preparations containing some corticosteroid hormones and the pharmacopeial methods don't report any method for the determination of these drugs either in presence of their degradation products or in presence of corticosteroid hormones.In this study simple, rapid precise and selective densitometric and HPLC method for the determination of some antifungal drugs KT, CL, MN, and EN in pure form or in the presence of their degradation products were developed. The methods were successfully applied to determine these drugs in pharmaceutical dosage forms and in presence of some corticosteroid hormones. ExperimentalMaterials and Reagents Ketoconazole (KT) Sedico Pharmaceutical Co., 6 October City-Egypt. The purity of the sample was found to be 99.82Ϯ1.157 applying a non-aqueous titration pharmacopoeial method. 3)Clotrimazole (CL) Pharcopharmaceuticals, Alexandria-Egypt. The purity of the sample was found to be 99.87Ϯ1.856 applying a non-aqueous titration pharmacopoeial method. 3)Miconazole nitrate (MN) Minapharm-Egypt. The purity of the sample was found to be 99.776Ϯ1.695 applying a non-aqueous titration pharmacopoeial method. Control and Research; Cairo, Egypt. Received February 26, 2007; accepted September 30, 2007; The HPLC method determined mixtures of CL or EN with their degradation products which were separated and quantified on a Zorbax C8 column. Elution was carried out using methanol : phosphate buffer pH 2.5 (65 : 35 v/v) as a mobile phase at a flow rate of 1.5 ml/min and UV detection at 220 nm for CL. For EN, a mixture of methanol : water containing 0.06 ml triethylamine pH 10 (75 : 25 v/v) was used as a mobile phase at a flow rate of 1.5 ml/min and UV detection at 225 nm. ...