الفهرس 
General IntroductionOnly 14 pages are availabe for public view
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Abstract
Electrochemical analysis become very common and promising in pharmaceutical analysis comparing with chromatographic technique due to the complicated procedures of chromatographic methods and the high cost of the organic solvents that required for HPLC measurements. In electrochemical techniques, developing of new sensors based on nano-materials is the secret key to enhance the sensitivity of the method. The presence of such nano-materials on the electrode surface enhances the conductivity, electroactive surface area, electron-transfer kinetics as well as reduces over-potential and causes redox reactions to become kinetically feasible. Therefore, such electrochemical sensors can be used extensively in quality control and in medical and environmental analysis. The metal and metal oxide nanoparticles gave a great result after mixing with graphene or with graphene like structures such as reduced graphene oxide (rGO) and activated charcoal (ACH). Nickel oxide and silver NPs occupied an effective rule in the nanosensors construction and electroanalytical applications due to their high electrical conductivity and electrocatalytic activity. So, the main aim of this work is developing some new electrochemical nanosensors based on activated charcoal nanosheets (ACH), NiO NPs, {ACH-NiO} nanocomposite, Ag NPs-reduced graphene nanocomposite {Ag@-rGO} and the ternary nanocomposite {ACH/Ag@rGO} as platforms of carbon paste electrode (CPE) for detection and quantification of “Ledipasvir” and “Prucalopride” drugs in pure form, pharmaceutical formulations and in biological fluids. The second aim is optimization and application a simple and effective HPLC method for detection and quantification of the drugs under interest and statistically compares its results with those of the described SW-AdASV method. The in-vitro dissolution/pharmaceutical equivalence of the available pharmaceutical dosage forms of such drugs and their acid, base and oxidation force degradation were also studied. II This thesis comprises of three main chapters: Chapter I: It contains the general introduction concerning the principles of the voltammetric techniques, types of working electrodes, and short notes about the chemical modifiers used in this Thesis. Chapter II: It contains the descriptions of the apparatus, materials, reagents, nature of drug compounds under consideration and their formulations which used in this study. Preparation of NiO NPs and {Ag@rGO} nanocomosite, buffer solutions, electrodes, drug and their tablet solutions was also well covered. The voltammetric and HPLC procedures used for assay of the investigated drugs in their bulk forms, formulations and in spiked human plasma were also presented in this chapter. Chapter III: This chapter contains the results and discussion of the electrochemical detection and quantification studies comparing to HPLC method of each of the examined drug. Some of the obtained results can be summarized in the following four parts: 3.1. Utilizing the Synergetic Benefit of the Novel Platform [NiO (Nano Flakes) /Activated charcoal (an alternative of graphene) for Adsorptive Stripping Voltammetric Determination of chronic Hepatitis C Virus Inhibitor Ledipasvir in its Harvoni® Tablets and in Human Plasma This research will open up a new application of activated charcoal (ACH) in electroanalytical chemistry. Fully characterization of ACH indicates that it can be promising used as an alternative material of graphene. This is due to its natural carbon material, low cost, extensive sources, nano and few layer structure (3-8 layers of interlayer distance of 0.37 nm), porous structure, high surface area, edge-plane-like defective sites, and few oxygenated functional groups. Besides, highly-crystallized NiO nano-flakes with a mean crystallite size of 14 nm and interplanar distance of 0.21 nm were synthesized. NiO NFs-ACH/CPE exhibited excellent electrochemical response for III the determination of “Ledipasvir” drug with good sensitivity and a low detection limits of 1.91×10-10 M and 5.49×10-10 M in bulk and human plasma samples. This part was published in: Journal of the Electrochemical Society, Volume 167, Number 11 (2020) 3.2. RP-HPLC Method for Simultaneous Determination of approved Sofosbuvir and Ledipasvir in tablet Dosage Form and its application in plasma and in-vitro dissolution assessment of its commercially available tablets A new simple RP-HPLC method was developed for the simultaneous determination of Sofosbuvir (SOF) and Ledipasvir (LED) in bulk, its pharmaceutical dosage forms and in human plasma. This separation was performed on Agilent Column Eclipse XDB C-18 , 5μm , 4.6*150 mm as stationary phase using gradient elution with a mobile phase of acetonitrile and 0.05 M Ammonium acetate pH 4.5 at a flow rate of 1.0 mL min-1 at a detection wavelength 245 nm. The method was validated according to the requirements of ICH Q2 (R1) guidelines. The method was linear over the range of (0.5 to 20 μg mL-1) and (0.05 to 20 μg mL-1) for SOF and LED in spiked human plasma, respectively. The limit of detection (LOD) for SOF and LED in human plasma was 0.026 μg mL-1 (4.90×10-8 M) and 0.015 μg mL-1 (1.68×10-8 M), respectively. The method was also successfully applied for the assay of SOF and LED in its commercial tablet dosage forms and its results were compared with those obtained from the proposed SW-AdASV method. In-vitro dissolution or pharmaceutical equivalence of the pharmaceutical dosage forms of SOF and LED under the name Harvoni® film coated tablets (as an innovator products) and Sofolanork plus film coated tablets (as a generic products) as well as their degradation test were also studied. IV 3.3. Activated charcoal/reduced graphene oxide-silver nanocomposite (ACH/Ag@rGO) as novel platform for sensitive prucalopride detection in human samples An electrochemical sensor based on {ACH/Ag@rGO} nanocomposite was prepared for voltammetric determination of “Prucalopride” drug. The morphology and structure of this composite were characterized. The electrochemical behavior of Prucalopride was investigated by cyclic voltammetry. Prucalopride was determined in the range of 5×10-9 – 1.0×10-6 M with limit of detection of 7.95×10-10 M using SWAdASV under optimization conditions. This electrode has good and satisfactory results in the determination of Prucalopride in its commercial formulations and human plasma. 3.4 RP-HPLC method for determination of Prucalopride and its application in In-vitro dissolution assessment of its commercially available tablets Simple RP-HPLC method was developed for determination of Prucalopride in bulk form and in its pharmaceutical dosage forms. Thermo Column BDS C18, 5μm, 4.6*150 mm, was used as the stationary phase for this separation. Isogradient elution was used with an acetonitrile and 0.01 M phosphate buffer pH 4.5 as the mobile phase, with a flow rate of 1.0 mL/min at a detection wavelength of 225 nm. The procedure was validated in accordance with ICH Q2 (R1) standards. The approach has a linear range of (1 to 20 μg mL-1). The limit of detection of 0.02 μg mL-1 (5.44 x10-8 M) and quantification of 0.08 μg mL-1 (2.17×10-7 M) were achieved. Also, In-vitro dissolution and force degradation of the pharmaceutical dosage forms of Prucalopride under the name “Resolor®” film coated tablets (as an innovator products) and “Conistova” film coated tablets (as a generic products); each tablet contains (2 mg Prucalopride) were also studied.