Spectrophotometric Methods for the Determination of Ketoconazole in Pharmaceutical Dosage Forms

Purpose: To develop simple, sensitive and economical methods for the determination of (KZ) in both pure samples and pharmaceutical formulations.
Methods: The first method (A) was based on the oxidation of the studied drug by a known excess of cerium (IV) as an oxidizing agent and subsequent determination of unreacted oxidant by reacting it with indigo carmine (IN) dye. The second method (B) involved potassium permanganate as oxidant and methylene blue (MB) as dye. Spectrophotometry was used to determine the residual amount of the dyes by measuring the absorbance of the two dyes at 610 and 660 nm, respectively. Comparison was made with the British Pharmacopoeia 1998 method.
Results: Linear calibration graphs were obtained at 4 - 30 and 5 - 35 μg/ml for the two methods at 610 and 660 nm, respectively. The regression equation was Y = 0.01X + 0.133, (R² = 0.996, RSD = 78 % and limit of detection (LOD) of μg/ml for method A. For the second method (B), it was Y = 0.008X + 0.039, (R² = 0.995), RSD = 0.95 % and LOD = 2.3 μg/ml. The proposed methods were successfully applied to the determination of KZ in pharmaceutical formulations.
Conclusion: The results demonstrate that the methods are as accurate and reproducible as official methods.

Keywords
Ketoconazole; Spectrophotometry; Cerium; Permanganate; Indigo carmine; Methylene blue