ANALYTICAL SCIENCES 2001, VOL.17 SUPPLEMENT i867 2001 © The Japan Society for Analytical Chemistry A New Spectrophotometric Method for the Determination of Ketoconazole Based on the Oxidation Reactions Khalil FARHADI † and Ramin MALEKI Department of Chemistry,Faculty of Science,Urmia University,Urmia,Iran(E-mail: kh.farhadi@mail.urmia.ac.ir) A new spectrophotometric method is proposed for the determination of ketoconazole in pharmaceutical preparations. The method is based on the coupled redox-complexation reactions, which proceed in the ketoconazole-iron (III) and 1,10-phenanthroline systems. A linear calibration graph was obtained between 1.6-16.0 ppm of ketoconazole. The proposed method is simple, rapid and sensitive. The procedure was successfully applied for the determination of ketoconazole in tablet, cream and shampoo samples. (Received on August 9, 2001; Accepted on September 13,2001) Ketoconazole,cis-1-acetyl-4-[4-[2-(2,4-dichlorophenyl)-2-(1H- imidazole-1-ylmethyl)-1,3-dioxolon-4-yl] methoxy piperazin (KC), is a highly effective broad spectrum antifungal agent. It is used to treat a wide variety of superficial and systematic mycoses 1,2 and has the advantage over other imidazole derivatives of producing adequate sustained blood levels following oral administration. 3 Moreover, it has been found that ketoconazole may cause changing in cytochrome P-450 dependent monooxygenase activities, 4,5 as well as in epoxide hydrolase. 6 Thus, the determination of ketoconazole in biological specimens and dosage forms has been the subject of considerable interest. Due to the vital importance of ketoconazole determination in pharmaceutical preparations and in biological fluids, several chromatographic, 3,7-12 spectroscopic 13-20 and electrochemical methods 21-25 for its quantitative determination have been reported. However, some of these methods need expensive equipment and/or are time consuming. In this article, we report a new simple, sensitive and inexpensive method for the determination of KC from pharmaceutical preparations. CH 3 C N N O .. CH 2 O CH 2 N N O O .. .. Cl Cl Ketoconazole (KC) We have recently studied the electrooxidation of KC in aqueous and non-aqueous media. 22-24 Based on the electrochemical results obtained, it was found that KC is initially oxidized reversible with the loss of one electron to KC ·+ cation radical, which can be stabilized by resonance, results in the observed pink-red color product. The stability of the cation radical is completely dependent to conditions of solution, so that it gradually decays via a chemical reaction in polar solvent and/or in weak acidic aqueous media. 22-24 Also, we found that, KC ·+ can be further oxidized with the loss of the second electron to give some stable products. 22,24 On the basis of results mentioned above, we were interested to investigate the chemically oxidation of KC in solutions in order to develop a spectrophotometric method for the determination of KC. In the present work, a new spectrophotometric method was developed for the determination of KC based on the coupled redox-complexation reaction, which proceed in the KC-Fe(III) and 1,10-phenanthroline system. The resulting colored complex between Fe(II) and 1,10-phenanthroline was determined at 512 nm. Experimental Apparatus A LKB model 4054 UV-Vis recording spectrophotometer equipped with 10 mm matched silica cells was used for all spectral measurements. The pH values were determined with a WTW moltilab 540 Ionalyzer (Germany) pH/mV meter using a combined electrode. Reagents All of the chemicals used in this study were of the highest purity available and used without further purification. Triply distilled water was used throughout. Reagent grade ketoconazole and its tablets, creams containing 200 mg and 2% of the drug were obtained from Behvazan pharmaceutical Company, Rasht, Iran. Ketoconazole shampoo samples (2%) was a pharmaceutical preparation from Shapha Pharmaceutical company, Tehran, Iran. Analytical grade 1,10-orthophenanthroline, FeCl 3 and Cetyltrimethylammonium bromide (CTAB) were purchased from Merck Company. A working standard solution of 0.001 M of KC was prepared by dissolving 0.0267 g of pure drug in 50 ml of water containing a few drop of hydrochloric acid (about 0.04 M) followed by further diluting of 5 ml of this solution to 50 ml. General Procedure An accurate ml volume of standard or sample solution containing an appropriate amount of ketoconazole was pipetted