الفهرس 
1.IntroductionOnly 14 pages are availabe for public view
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Abstract
The thesis comprises five main parts:
Part I : This part includes a general introduction regarding the chemical names, structures, molecular weight, physical properties and pharmacological actions and uses of the studied nutraceuticals and drugs in the thesis.
Part II : This part presents different methods analyzing illicit nutraceuticals, NTCs, in different products as honey and tablets made from herbal extracts.
For illicit NTCs claimed to enhance sexual performance, synthetic drugs (sildenafil, tadalafil, avanafil, vardenafil and dapoxetine) are common adulterants, so they were selected to be simultaneously analyzed in the current study.
Moreover, as natural aphrodisiacs (icariin and yohimbine) are claimed to be present in many of these illicit NTCs, they were also included in the study.
Three liquid chromatographic methods (HPLC-FLD, HPLCDAD and UPLC-MS) were developed and validated for the determination of the selected drugs and the natural aphrodisiacs.
HPLC with fluorescence detection enables rapid and reliable determination of natively fluorescence yohimbine, tadalafil vardenafil and dapoxetine and it is the first report to analyze these compounds as adulterants in illicit NTCs.
Although diode array detector (DAD) enables the analysis of the seven compounds, fluorescence detector (FLD) shows better sensitivity and selectivity with lower LOQ and LOD.
On the other hand, UPLC-MS offers the advantages of peak identity confirmation, comparable sensitivity and selectivity with HPLC-FLD and not restricted to certain compounds as HPLC-FLD.
One or more of the selected synthetic drugs were found in the analyzed NTCs while natural aphrodisiacs were absent.
Part III : In this part a novel, sensitive and simple HPLC method hyphenated to fluorometric detector (FLD) was developed for the determination of Doxorubicin Hydrochloride (DXR) and prodigiosin (PDG) in rat plasma.
The chromatographic conditions were optimized to achieve the highest performance parameters.
The method was validated according to the FDA guidelines with respect to system suitability, selectivity, linearity, accuracy, precision, matrix effect, carryover and stability.
The purity of the DXR and PDG peaks were confirmed using the DAD.
The sample pre-treatment involves a protein precipitation with acetonitrile with satisfying extraction efficiency.
Doxorubicin (DXR) is one of the most potentchemotherapeutic drugs against a broad range of malignant tumors as solid tumors, lymphoma and transplantable leukemias but with induced cardiotoxicity.
Prodigiosin, having an effective anti-cancer activity, could be entrapped with doxorubicin in a nano micelle protein, casein, for developing a novel drug delivery system.
This adjuvant therapy along with biocompatible, biodegradable and safe casein can provide a synergistic anticancer effect and thus decreasing DXR dose and its threatened side effects.
Moreover, the selected micelle form as a delivery system has the ability to incorporate the hydrophobic PDG rendering it more hydrophilic to be applied intravenously.
As the proposed method has been validated, it was subsequently implemented to evaluate this nano system after intravenous injection in healthy rats.
A comparative pharmacokinetics’ study for DXR was carried out in healthy male rats in free form, entrapped alone in the nano micelle and entrapped with PDG in the nano micelle.
After testing the differences in pharmacokinetic parameters of the different formulations using ANOVA, the results showed insignificant differences among the tested parameters.
This indicates that the presented nano delivery system has succeeded to incorporate PDG and DXR in a hydrophilic, safe and potent formulation with confirmation of cytotoxic activity.
Both PDG and casein have negligible effect on the distribution and elimination of DXR.
Part IV : This part describes the development and validation of a new, reliable, sensitive and new LC-MS method for the bioassay of silymarin (SLY), ledipasvir (LED), sofosbuvir (SOF) and its inactive metabolite: GS-331007 in spiked rat plasma with LLOQ 10, 1, 4 and 10 ng/mL, respectively.
As the emergence use of NTCs as silymarin (SLY) for liver support in HCV patients, sometimes coincides with the administration of ledipasvir (LED) and sofosbuvir (SOF) to eradicate the virus.
This recalls for a deep investigation of these NTCs effects on the pharmacokinetic (PK) parameters of these antiviral drugs to ensure their safety and efficacy during their concomitant use in HCV treatment.
So, in this study, silymarin (SLY) was given orally to healthy male rats with sofosbuvir (SOF) and ledipasvir (LED) and any alteration in PK parameters in these drugs and in GS-331007 were investigated using the validated LC-MS.
It was found that SLY induced inhibition of SOF nd LED hepatic uptake associated with a decreased metabolism appeared in GS-331007 AUC.
Such circumstances render the patient exposed to an unplanned high serum concentration of SOF with a possible decrease in efficacy potentially leading to therapeutic failure and the emergence of viral resistance.
Part V :
This part reviews different analytical strategies for the assessment of recently approved direct acting antiviral drugs.
Among many direct-acting antiviral drugs (DAADs) targeting non-structural proteins, a special focus was given for those targeting hepatitis C virus and Coronavirus: sofosbuvir, ledipasvir, grazoprevir, glecaprevir, voxilaprevir, velpatasvir, elbasvir, pibrentasvir and remdesivir.
The last one is indicated for COVID-19, while the rest are indicated for HCV treatment.
This review highlights the current approaches, published in the period between 2017 to present, dealing with the determination of these drugs in two different matrices: pharmaceuticals and biological fluids with the challenges of analyzing these drugs either alone, with other drugs, in presence of interferences (pharmaceutical excipients or endogenous plasma components) or in presence of matrix impurities, degradation products and metabolites.
These approaches include spectroscopic, chromatographic, capillary electrophoretic, voltametric and nuclear magnetic resonance methods that have been reported during this period.
Moreover, the analytical instrumentation and methods used in determination of these DAADs is illustrated in tabulated forms.
The thesis consists of 167 pages and comprises tables, figures and 308 references.
It ends with an Arabic summary.
Also, it contains list of abbreviations, 35 tables and 28 figures in the beginning of the thesis.