الفهرس 
Part I: General IntroductionOnly 14 pages are availabe for public view
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Abstract
Based on the alarming COVID-19 proliferation, the goal of the current thesis is to design and validate efficient, sensitive and green spectroscopic and chromatographic approaches for determining three antiviral agents including; favipravir, remdesivir and ribavirin in raw material, pharmaceuticals and human plasma. The thesis is divided into six parts.
Part I: General Introduction.
This part presents a general overview of antiviral agents and the studied drugs such as chemical structure, properties and pharmacological effects. It also involves a study of the literature regarding analytical techniques published for determining the investigated drugs in pure form, pharmaceuticals, and/or biological fluids. At the end of this part, the aim of the suggested work was discussed.
Part II: Spectrofluorimetric Determination of the Anti-Covid 19 Agent; Remdesivir in Vials and Spiked Human Plasma.
In this part, two sensitive, simple and green spectrofluorimetric methods have been developed to determine REM in pharmaceutical formulation, in addition to, spiked human plasma. The technique involves measuring the REM’s native fluorescence in distilled water at 410 nm following excitation at 241 nm, giving a linear relationship over the range 50 – 500 ng/mL, and then improving the sensitivity of REM through micellar formation using 2 % w/v sodium dodecyl sulfate (SDS). A linear relationship has been obtained over the range 10 – 350 ng/mL having detection and quantitation limits of 2.34 and 7.1 ng/mL, respectively. Different analytical parameters have been carefully studied. A validation study has been conducted successfully in accordance with ICH guidelines. The developed methods’ greenness was assessed utilizing a greenness profile and analytical Eco-scale standards. Both methods were discovered to be environmentally friendly and could be successfully used for the determination of the studied drugs in pharmaceutical formulation and human plasma with good accuracy and high precision. As a result, the developed spectrofluorimetric methods could be ideally suited for determination of REM in quality control and medicinal laboratories.
Part III: Simultaneous Sensitive Determination of Anti COVID-19 Drugs ’’Favipiravir and Remdesivir’’ in Raw Materials and Pharmaceuticals by Different Spectrophotometric Methods with Green Assessment.
This part introduces four sensitive, easy, accurate and green spectrophotometric methods for determination of FAV and REM without prior separation. In the first method FAV was quantified in zero order directly at 361.8 nm while, REM was obtained using absorption correction method at 241 nm after computing FAV’s equality factor. In the second method, both FAV and REM were determined by dual wavelength method using absorbance difference between (235.8 and 248.2 nm) and (244.8 and 228.8 nm), respectively. While in the third method, FAV and REM were determined by first derivative method at 380 nm and 237.2 nm, respectively. Finally in the fourth method, FAV was determined by first derivative of ratio spectra method (1DD) using standard spectrum of 20 μg/mL of REM as a divisor at 258.8 nm. By the same way, REM was obtained using standard spectrum of 30 μg/mL of FAV as a divisor at 290 nm. The developed methods were successfully validated according to ICH guidelines with good accuracy and precision affording the required sensitivity and linearity range needed for daily quality control analysis (1.5 - 30 µg for FAV and REM). Also, they were effectively applied to pharmaceutical formulations and laboratory prepared mixtures. The results obtained by developed methods were statistically compared with reported ones and no significant difference was found. Additionally, various greenness assessment metrics were used to assess the effectiveness and impact on human health including; Eco-Scale, NEMI, modified NEMI, GAPI and AGREE. Findings have been obtained demonstrate the ecological impact of these methods.
Part IV: Novel Environment Friendly TLC-Densitometric Method for Determination of Anti-Coronavirus Drugs “Remdesivir and Favipiravir”: Green Assessment with Application to Pharmaceutical Formulations and Human Plasma.
Herein, a green, sensitive, and selective densitometric method has been proposed and validated for determination of REM and FAV in pharmaceutical formulations and spiked human plasma on normal phase TLC plates. A solvent mixture of ethyl acetate-methanol-ammonia (8 :2 :0.2 by volume) has been chosen as developing mobile phase system. Well resolved spots have been detected at 235 nm with retardation factors (Rf) of 0.15 and 0.81 for FAV and REM, respectively. A validation study has been carried out in the light of ICH guidelines with good linearity in the concentration rangers of 0.08 – 5 and 0.2 – 4.5 µg/band for FAV and REM, respectively and excellent sensitivities with quantitation limits down to 0.019 and 0.04 μg/band, respectively. The developed method has been successfully applied to pharmaceutical formulations and spiked plasma with excellent recoveries ranged from 97.21 to 101.31%. Moreover, the obtained results were compared to previously reported methods using variance f-test and student’s t-test and no significant differences were observed. The greenness of the method has been evaluated using the standards of greenness profile, Eco-Scale and Green Analytical Procedure Index.
Part VI: Nano-Fluorescent Quantum Dots as Substrates for Determination of Ribavirin in Pharmaceuticals and Human Plasma as well as Monitoring of its Kinetic Interaction with Salmon Sperm DNA.
In this part, RIB was successfully determined by fluorescence quenching upon its interaction with environmentally friendly phosphorus and nitrogen co-doped quantum dots (PNQDs) as a fluorescent probe synthesized from pure orange juice as natural source doped with ethylenediamine and orthophosphoric acid which were subjected to full characterization. Different analytical parameters affecting the fluorescence spectra have been optimized and validated in accordance to the ICH guidelines. The proposed method has provided an efficient tracing of the interaction between RIB molecules and the synthesized QDs in an acidic medium (off-mode). The RIB molecule has shown excellent sensitivity at λem of 401 nm upon excitation at 245 nm throughout a linear range; 0.06 - 10 µg/mL. The proposed method has provided high sensitivity for detection and quantitation limits down to 14 and 40 ng/mL, respectively. The quenching mode achieved by RIB was proven to be static in raw samples and samples extracted of spiked plasma. The proposed method has been successfully applied for determination of RIB in the commercial capsules and spiked human plasma samples with good recovery percentages. Interestingly, these carbon dots have been utilized as nano-fluorescent platforms for assessment of the binding interaction kinetics between the RIB molecules and ssDNA. This has been implemented through peeling off the RIB molecules from surface of the PNQDs upon successive addition of the ssDNA, the fluorescence restoration (turning-on) as successful monitoring of its antimicrobial potency. It was evidenced a strong binding interaction with a binding constant of 2.38×104 mol-1/ L. Significantly, this could open doors for an extended application for on-site monitoring of RIB as well as its interactions with biomolecules and microorganisms.