الفهرس 
general introduction and analytical review
chpter 1: using iodine as 0- acceptorOnly 14 pages are availabe for public view
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Abstract
This thesis is concerned with the spectrophotometric and spectro-fluorimetric analysis of five antifungal drugs namely, clotrimazole, econazole nitrate, ketoconazole, miconazole and tolnaftate. The thesis comprises three parts in addition to general introduction about the antifungal drugs especially the selected drugs and the different official and reported methods described for the assay of these drugs.
Part I
Chapter 1
A simple, rapid, accurate and sensitive spectrophotometric method is developed for the determination of the imidazole antifungal drugs; clotrimazole, econazole nitrate, ketoconazole and miconazole. The method is based on the interaction between the tertiary amine moiety of the imidazole drugs (pyridine-nitrogen) as the n-electron donor and iodine as a-acceptor, in 1,2-dichloroethane to form a stable coloured charge-transfer complex. The absorbance is measured at 290 run for all studied drugs. A study for all the reaction variables has been conducted to optimize the reaction conditions.A linear relationship between the absorbance and concentration occurred within the range 1-40 ug/ml at 290 nm for all studied imidazole drugs. The limit of detection was ranged from 0.18 to 1.47 jig/ml. The molar ratio of iodine to each of the tested drugs is 1:1 except for ketoconazole is 2:1. The antithyroid activities of these drugs was predicted by the determination of the association constants of their complexes with iodine. In addition, the free energy change (AG°) was determined for all drugs. The proposed method was satisfactorily applied to the analysis of commercial dosage forms of the tested drugs and compared with the reported method.
Chapter 2
Two simple, and accurate spectrophotometric methods are suggested for the determination of the imidazole antifungal drugs. Both methods are based on the interaction between the tertiary amine moiety of the imidazole drugs (pyridine-nitrogen) as the n-electron donor and the n-acceptors, 2,3-Dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) in methanol or acetonitrile respectively. Optimal conditions for colour formation were determined for both methods.The produced colour obeys Beer’s law for all studied imidazole antiftmgal drugs at 460 and 843 nm for DDQ and TCNQ-methods respectively. The molar ratio of DDQ to each of the tested drugs is 2:1 while the molar ratio of TCNQ to each of the tested drugs is 1:1.The application of this procedure to the determination of all studied drugs in pure as well as in certain pharmaceutical preparations are given.
Part II
This part is concerned with the developement of a colourimetric method for the determination of clotrimazole, econazole, ketoconazole andI miconazole. The method is based on the interaction of p-chloranilic acid with the above drugs in acetonitrile producing a purple coloured chromogen measured at 520 nm.Investigations were carried out to study the reaction variables. Under the established conditions, concentration was found to be proportional to absorbance of the chromophore produced by the reaction of p-chloranilic acid with each studied drug. Beer’s law is obeyed in the concentration range of 30-300 p.g/ml. The limit of detection is ranged from 2.39 to 4.47 jig/ml. The molar ratio of p-CA to each of the tested drugs is 1:1. The proposed method was successfully applied to the determination of all studied drugs in their pharmaceutical formulations.
Part III
This part involved the development of two spectrofluorimetric methods for the determination of ketoconazole and tolnaftate and a spectrophotometric method for the determination of tolnaftate.A highly selective and sensitive spectrofluorimetric method for the determination of ketoconazole was developed. The method is based on measurement of the native fluorescence of ketoconazole in Teorell and Stenhagen buffer, pH 10, at 375 nm with excitation at 288 nm. A study for all variables has been carried out to optimize the reaction conditions. Fluorescence intensity versus concentration is linear up to 800 ng/ml, the lower limit of detection is 15 ng/ml under the studied conditions. The proposed method was applied to the analysis of commercial dosage forms of the tested drug.A spectrofluorimetric method was developed for the determination of tolnaftate. The method is based on measurement of the fluorescence after alkaline hydrolysis with 5 M NaOH solution at 420 nm with excitation at 344 nm. A study for all variables has been conducted to optimize the reaction conditions. A linear relationship between the fluorescence intensity of the hydrolytic product of tolnaftate and concentration has been occurred. The linear range was 50-400 ng/ml with lower limit of detection 6.8 ng/ml. The suggested method was successfully applied to the analysis of tolnaftate in single as well as in multicomponent formulations without interference.A spectrophotometric method for the determination of tolnaftate was also developed. The method depends on measurement of the absorbance at 280 or 344 nm after alkaline hydrolysis of tolnaftate with 5 M NaOH solution. The absorbance obeys Beer’s law in a concentration range of 5-70 /ig/ml with lower limit of detection 0.96 jug/ml.Several commercial pharmaceutical preparations were satisfactorily analysed for their tolnaftate content by the developed method.