الفهرس 
Part I: General introductionOnly 14 pages are availabe for public view
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Abstract
In this thesis, four alpha blocker drugs namely doxazosin mesylate, alfuzosin, terazosin and tamsulosin hydrochloride, have been determined using different spectrophotometric and spectrofluorimetric techniques in its pharmaceutical preparation and human plasma.
The presented thesis falls in five parts:
Part I: General Introduction
This part provides a general introduction about the investigated compounds such as, pharmaceutical importance, chemical structure and analytical review for the analytical techniques used for the determination of the studied drugs in pure forms, dosage forms or in biological fluids. At the end of this part, we described the objective of the suggested work.
Part II: Highly sensitive spectrofluorimetric method for determination of doxazosin through derivatization with fluorescamine; Application to content uniformity testing.
A highly sensitive, simple and selective spectrofluorimetric method has been developed and validated for determination of doxazosin mesylate in pure form, pharmaceutical formulation and human plasma. The method is based on the reaction between doxazosin mesylate and fluorescamine in Teorell buffer solution (pH 3) to give highly fluorescent derivative that can be measured at 489 nm using excitation wavelength of 385 nm. Different experimental parameters affecting the reaction were carefully studied and optimized. The calibration plot was constructed over the concentration range of 16.0 – 400.0 ng mL−1 with quantitation limit of 14.3 ng mL−1. The developed procedure was validated according to ICH guidelines and the results were satisfactory. The proposed method has been successfully applied to the analysis of the cited drug in its pharmaceutical preparations as well as for content uniformity testing. The results showed excellent agreement with the reported method with respect to precision and accuracy. In addition, the drug concentration was determined in the spiked human plasma by the suggested method with high accuracy.
Part III: Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin bulk, dosage forms and human plasma
This part is devoted to develop of new highly sensitive, cheap, simple and accurate spectrofluorimetric method for determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and human plasma. The developed method is based on the reaction of primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to Hantzsch reaction producing yellow fluorescent products, measured at 480 nm after excitation at 415nm. The different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over the concentration range (70 - 900 ng mL-1) with quantitation limits 27.1 and 32.2 ng mL-1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied for the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy.
Part IV: Highly sensitive micelle-enhanced spectrofluorimetric method for determination of Doxazosin, Alfuzosin, and Terazosin in real human plasma.
This part is concerned with the development a simple rapid, highly sensitive and cheap spectrofluorimetric method for the determination of Alfuzosin hydrochloride (ALF), Doxazosin mesylate (DOX) and Terazosin hydrochloride (TER) in pure forms and real human plasma. The proposed method is based on micelle enhancement of studied drugs with polyoxyethylen 50 stearate (POE50S) micellar system. The method showed an excitation at 325, 340 and 250 nm for alfuzosin, doxazosin and terazosin respectively, and emission maxima at 382 nm. The fluorescence intensity-concentration plots of doxazosin, alfuzosin and terazosin were rectilinear over the concentration ranges (2.0 – 60.0 ng mL-1) for DOX and (4.0 - 100.0 ng mL-1) for ALF and TER. The proposed method was validated according to ICH guidelines and has been successfully applied for the analysis of these drugs in their pharmaceutical preparations as well as for content uniformity testing and the results showed an excellent agreement with the reported methods, indicating no significant difference in accuracy and precision. The proposed method was successfully applied for the analysis of the cited drugs in real human plasma with high accuracy
Part V: Highly sensitive spectrofluorimetric and spectrophotometric methods for determination some alpha-blockers using ninhydrin
This part is devoted to develop a simple, accurate, highly sensitive spectrofluorimetric and spectrophotometric methods for determination of alpha blocker drugs. The first method based on condensation reaction of doxazosin mesylate (DOX), alfuzosin hydrochloride (ALF) and terazosin hydrochloride ( TER) with 0.1 % ninhydrin in presence of phenylacetaldehyde producing highly fluorogenic product measured spectrofluorometrically at 476 nm (λex = 395 nm), within concentration range (50.0 – 400.0) ng mL-1 for ( DOX and ALF), and (60.0 – 400.0) ng mL-1 for (TER). The second method based on reaction of doxazosin mesylate, terazosin hydrochloride and tamsulosin hydrochloride (TAM) with 2 % ninhydrin in N, N’-dimethylformamide (DMF) producing Rhumann’s purple colored product with DOX and TER measured spectrophotometrically at 549 nm, and blue color with TAM measured at 598.5 nm, within concentration range (7.0 - 70.0), (5.0 - 50.0), (2.0 – 30.0) µg mL-1 for DOX, TER, and TAM, respectively. The proposed methods were successfully applied to the analysis of cited drugs in pure forms, pharmaceutical preparations, content uniformity test and spiked human plasma.
References
The thesis includes a list of 174 References.
In addition, the thesis comprises 44 tables, 36 figures and 5 schemes, as well as summary in English and Arabic.