الفهرس 
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Abstract
This Thesis Consisted Of Three Parts In Addition To References And An Arabic Summary. Each Part Includes An Introduction, Literature Review, Experimental Work For The Studied Compounds, Results, Discussion And Ended With A Conclusion.
PART I: Quantitative Determination Of Dimenhydrinate, Cinnarizine, And Their Toxic Impurities
This Part Included Four Sections.
SECTION A: Introduction, Literature Review, And In-Silico Toxicity Study
This Section Included An Introduction About The Pharmacological Action Of Dimenhydrinate (DMH) And Cinnarizine (CIN). It Also Included Their Chemical Structures, Physical Properties, And A Summary Of The Methods Published For Their Analysis In Their Formulations And Biological Samples. Besides, It Included In Silico Toxicity Study Of The CIN Impurities, The Structure, And Toxicities Of Benzophenone (BZP), The Official Impurity Of DMH.
SECTION B: Chemometric Assisted Spectrophotometric Methods For Simultaneous Determination Of Dimenhydrinate, Cinnarizine, And Their Toxic Impurities
In This Section, Four Chemometric Methods; PLS, GA-PLS, ANN, GA-ANN Had Been Developed And Applied For Determination Of The Quaternary Mixture (DMH, CIN, BZP, And DPP) Using Methanol As A Solvent. The Used Spectral Range Was 230.0-294.0 Nm. A Training Set Of 25 Mixture Containing Different Ratios Of The Mentioned Components Were Used For The Construction Of The Four Models. Genetic Algorithm Was Used To Exclude Inherent Wavelengths And To Choose Only Relevant Ones. The Specificity Of The Proposed Models Was Checked Using Laboratory Prepared Mixtures (External Validation Set Of Five Mixtures). Satisfactory Results Were Obtained On Applying The Developed Methods For Analysis Of DMH And CIN In Amocerebral Plus® Tablets. The Four Developed Methods Were Compared With Each Other And Statistically Compared To Reported Method.
SECTION C: TLC-Densitometric Method For Simultaneous Determination Of Dimenhydrinate, Cinnarizine, And Their Toxic Impurities
In This Section, Novel TLC-Densitometric Method Had Been Developed And Applied For Simultaneous Determination Of DMH And CIN And Their Toxic Impurities; BZP And DPP, Respectively. The chromatographic Separation Was Obtained Using Hexane: Ethanol: Acetone: Glacial Acetic Acid (7.00: 3.00: 0.70: 0.50, By Volume) As A Mobile Phase At A Temperature Of 25◦C. The Separated Bands Were UV Scanned At 225.0 Nm. The Suitability Of The Proposed chromatographic Method Was Ensured By The Determination Of System Suitability Testing Parameters Of The Separated Drugs. The Developed Method Was Applied For The Analysis Of DMH And CIN In Amocerebral Plus® Tablets And Was Statistically Compared To Reported Method.
SECTION D: Experimentally Designed HPLC Method For Simultaneous Analysis Of Dimenhydrinate, Cinnarizine, And Their Toxic Impurities
In This Section, Novel HPLC Method Had Been Developed And Applied For Simultaneous Determination Of DMH And CIN And Their Toxic Impurities. Custom Experimental Design Was Used For Optimization Of The Critical Factors Affecting The Separation. The Optimum chromatographic Separation Was Achieved Using A Stationary Phase Of Xbridge® HPLC RP- C18 Column And Isocratic Elution The Mobile Phase Of Acetonitrile: 0.10% SLS W/V (90.00:10.00, V/V) Flowed At 2.00 Ml/Min. The Temperature Was Adjusted To 25OC, And The Effluent Was UV Scanned At 215.0 Nm. The Overall Run Time Was 13.06 Min. The Developed Method Was Applied For Analysis Of DMH And CIN In Amocerebral Plus® Tablets. where Good Results Were Obtained.
Greenness Assessment Tools: National Environmental Methods Index (NEMI), Analytical Eco-Scale, And Green Analytical Procedure Index (GAPI) Were Used For Greenness Profiling Of The Developed Methods In This Part. Besides, The Developed Methods Were Compared With Reported Methods For Determination Of DMH, CIN And DPP.
PART II: In Vivo Analysis Of Tinidazole And Ibuprofen: Application To Real Human Plasma Samples
This Part Included Three Sections.
SECTION A: Introduction And Literature Review
This Section Included An Introduction About The Pharmacological Action Of Tinidazole (TNZ) And Ibuprofen (IBU). It Also Included Their Chemical Structures, Physical Properties, And A Summary Of The Methods Published For Their Analysis In Their Formulations And Biological Samples.
SECTION B: TLC-Densitometric Method For Simultaneous Determination Of Tinidazole And Ibuprofen In Real Human Plasma Samples
In This Section, Novel TLC-Densitometric Method Had Been Developed And Applied For Simultaneous Determination Of TNZ And IBU In Plasma. The chromatographic Separation Was Obtained Using Ethanol: Ethyl Acetate: Ammonium Hydroxide Solution 33% (7.50: 2.50: 0.05, By Volume) As A Mobile Phase. The Separated Bands Were UV Scanned At 220.0 Nm And Cyclizine (CYC) Was Used As Internal Standard (IS). The Developed Method Was Applied For Simultaneous Determination Of TNZ And IBU In Real Plasma Samples Of Healthy Volunteers. The Suitability Of The Proposed chromatographic Method Was Ensured By The Determination Of System Suitability Testing Parameters Of The Separated Drugs.
SECTION C: HPLC Method For Simultaneous Determination Of Tinidazole And Ibuprofen In Real Human Plasma Samples
In This Section, A Novel HPLC Method Had Been Developed And Applied For Simultaneous Determination Of TNZ And IBU In Plasma Samples. The chromatographic Separation Was Obtained In A Gradient Elution Mode Using A Stationary Phase Of Xterra® C18 Column And A Mobile Phase A (Methanol), And Mobile Phase B (0.05 M Nah2p04) At Ph 8.0 Adjusted With Aqueous Naoh Solution. The Temperature Was Adjusted To 25OC And The Effluent Was UV Scanned At 220.0 For IBU And 330.0 Nm For TNZ. Sulphasalazine (SFS) Was Used As An Internal Standard (IS). The Developed Method Was Applied For Simultaneous Determination Of TNZ And IBU In Real Plasma Samples Of Healthy Volunteer And Method Validation Was Carried Out According To FDA Guidelines.
Greenness Assessment Tools: NEMI, Analytical Eco-Scale, And GAPI Were Used For Greenness Profiling Of The Developed Methods And They Were Compared With Reported Methods For Determination Of TNZ Or IBU In Plasma.
PART III: Electrochemical Determination Of The Biohazardous Compound; P-Aminophenol
SECTION A: Introduction And Literature Review
This Section Included The Chemical Structure, Physical Properties And An Introduction About The Sources And Toxicities Of P-Aminophenol (PAP). It Also Included A Summary Of The Methods Published For Its Analysis In Different Matrices.
SECTION B: Experimentally Designed Potentiometric Ion selective Electrode For Determination Of P-Aminophenol
In This Section, A Custom Experimental Design Was Constructed To Optimize An Ion selective Electrode Potentiometric Sensor For The Determination Of PAP In Different Matrices. Three Quantitative Factors (Ion Exchange %, PVC: Plasticizer Ratio And Membrane Thickness), A Qualitative Factor (Ionophore Type) And Five Responses (Slope, Limit Of Detection, Limit Of Quantification, Correlation Coefficient And Response Time) Were Used Through The Custom Design. The Optimized Sensor Included 1.25% Ion Exchanger, PVC: Plasticizer Ratio 1:4 And Calix-[8]-Arene As Ionophore In 0.07 Mm Thick PVC Membrane. It Showed A Nernstian Slope Of 61.93 Mv/Decade Over A PAP Concentration Range from 2.99×10-5-1×10-2M With LOD Of 2.86 ×10-5M. The Optimized Sensor Showed A Fast And Stable Response In A Ph Range Of 2.00-3.50. It Was selectively Used To Determine PAP In Pharmaceutical Formulations, Biological Fluids And Environmental Samples Without Pretreatment And In The Presence Of Common Interferents.