الفهرس 
Different Stability Indicating Analytical Methods for Determination of Paracetamol, Dantrolene Sodium, Their Toxic Impurities, and Degradation ProductsOnly 14 pages are availabe for public view
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Abstract
This Thesis Consists Of Three Parts, Containing Different Analytical Methods For Quantitative Determination Of Some Pharmaceutical Compounds Containing Carbonyl group Either In Their Pharmaceutical Formulations Or Synthetic Mixtures.
Part I: Different Stability Indicating Analytical Methods For Determination Of Paracetamol, Dantrolene Sodium, Their Toxic Impurities, And Degradation Products
This Part Is Concerned With Developing Sensitive, Accurate And Simple Chemometric And chromatographic Stability Indicating Methods For Determination Of Paracetamol (PAR) And Dantrolene Sodium (DNS) Without Interference from Their Toxic Impurities And Degradation Products. The Studied PAR Impurities Are The Genotoxic And Nephrotoxic P-Amino Phenol (PAP) And The Hepatotoxic And Nephrotoxic Chloroacetanilide (CHL). While, 5-(4-Nitrophenyl)-2-Furaldehyde (DEG) Is Reported To Be DNS Mutagenic And Carcinogenic Degradation Product.
Section A: Introduction And Literature Review
This Section Includes An Introduction About The Pharmacological Actions Of Paracetamol And Dantrolene Sodium, Their Chemical Structures, Physical Properties And Summary Of The Published Methods Developed For Their Analysis.
Section B: Determination Of Paractamol, Dantrolene Sodium, Their Toxic Impurities, And Degradation Products By Different Chemometric Methods
In This Section, Two Chemometric Models, Namely; Partial Least Squares (PLS) And Principal Component Regression (PCR) Have Been Developed For Determination Of PAR And DNS Along With Their Toxic Impurities And Degradation Products PAP, CHL And DEG In Pure Form And Dosage Form. Five Level Five Factors Calibration Design Was Performed Using 5 Concentration Levels. The Absorption Spectra Of The Mixtures Were Recorded In The Range Of 225–400 Nm And Then Transferred To Matlab® 7.1 For Data Analysis. The Developed Methods Were Successfully Applied For Quantitation Of The Studied Drugs In Dantrelax Compound® Capsules And The Standard Addition Technique Has Been Applied To Verify Their Validity.
Section C: Determination Of Paractamol, Dantrolene Sodium, Their Toxic Impurities, And Degradation Products By Different chromatographic Methods
In This Section, Simple, Sensitive And Reproducible TLC–Densitometric And HPLC Methods Were Developed For Simultaneous Determination Of PAR, DNS And Their Toxic Impurities And Degradation Products With High Accuracy And Short Analysis Time. For TLC-Densitometric Method, Chloroform: Ethyl Acetate: Acetic Acid: Triethylamine (7:3:0.5:0.05, By Volume) Was Used As The Developing System And 230 Nm As A Scanning Wavelength. While For HPLC Method, The Mixture Was Separated On C18 Column With A Mixture Of Methanol: Water (55:45, By V/V Ph=3 With Aqueous Formic Acid) As The Mobile Phase At Flow Rate Of 1 Ml/Min And UV Detection At 230 Nm. The Developed Methods Have Been Validated According To ICH Guidelines And Applied To Determine The Studied Drugs In Dantrelax Compound® Capsules. Additionally, The Methods Were Compared To All The Published chromatographic Methods And The Proposed Methods Were Found To Be Superior Regarding selectivity.
Part II: Quantitative Determination Of Chlorzoxazone, Diclofenac Potassium, And Chlorzoxazone Toxic Degradation Product By Different Analytical Methods
This Part Is Focused On Developing Different Specific, Sensitive, And Accurate Spectrophotometric And chromatographic Methods For Determination Of Chlorzoxazone (CHZ), Diclofenac Potassium (DIC), And Chlorzoxazone Toxic Degradation Product (ACP) In Pharmaceutical Formulation And Laboratory Prepared Mixtures. These Methods Were The First Developed Ones For Determination Of The Studied Components.
This Part Includes Three Sections:
Section A: Introduction And Literature Review
This Section Includes An Introduction About The Pharmacological Actions Of Chlorzoxazone And Diclofenac Potassium, Their Chemical Structures, Physical Properties And Summary Of The Published Methods Developed For Their Analysis.
Section B: Determination Of Chlorzoxazone, Diclofenac Potassium, And Chlorzoxazone Toxic Degradation Product By Different Spectrophotometric Methods
In This Section, Second Derivative (2D), First Derivative Of Ratio Spectra (1DD), Dual Wavelength And Ratio Difference Spectrophotometric Methods Have Been Developed And Optimized For Analysis Of CHZ, DIC, And ACP Using Naoh As A Solvent.
Second Derivative Spectrophotometric Method (2D) Was Used For Determination Of CHZ At 294.8 Nm. While, First Derivative Of Ratio Spectra (1DD) Was Used For Determination Of DIC And ACP At 282.4 And 265 Nm, Respectively. Dual Wavelength And Ratio Difference Spectrophotometric Methods Depended On Measuring The Absorbance Or Amplitude Difference At Two Points On The Spectra Or Ratio Spectra. Dual Wavelength Method Was Used For Determination Of CHZ And DIC At (280 And 274 Nm) And (228.2 And 253.4 Nm), Respectively. While, Ratio Difference Spectrophotometric Method Was Used For Determination Of ACP Using The Difference Between (260.8 And 270.2 Nm) And 10 Μg/Ml DIC As A Divisor. The Developed Spectrophotometric Methods Were Tested By Application To Laboratory Prepared Mixtures And Declophen Plus® Capsules. Validation Of The Methods Was Carried Out With Respect To ICH Guidelines.
Section C: Determination Of Chlorzoxazone, Diclofenac Potassium, And Chlorzoxazone Toxic Degradation Product By Different chromatographic Methods
In This Section, TLC–Densitometric And HPLC Methods Have Been Developed For Simultaneous Determination Of CHZ, DIC, And ACP In Their Ternary Mixture. For TLC–Densitometric Method, Chloroform : Ethanol : Triethylamine (9:1:0.1, By Volume) Was Used As The Developing System And 230 Nm As A Scanning Wavelength. While, A Mixture Of Methanol : Water : Ortho-Phosphoric Acid (75: 25: 0.05, By Volume) In Isocratic Mode Was Used As The Mobile Phase For HPLC Method At A Flow Rate Of 1 Ml/Min With UV Detection At 230 Nm And C8 Column. Separation Efficiency Was Tested By Calculation Of System Suitability Testing Parameters And All Results Were Within The Acceptable Limits. Also, selectivity And Validity Of The Methods Were Confirmed By Absence Of Interference from Capsules’ Additives.
Part III: Quantitative Determination Of Vildagliptin, Metformin, And Metformin Toxic Impurity (Melamine) By Different Analytical Methods
This Part Is Focused On Investigating Different Accurate And Simple Spectrophotometric And chromatographic Methods For Determination Of Vildagliptin (VIL), Metformin (MET), And Metformin Toxic Impurity Melamine; (MEL) In Pure Form And Galvus Met® Tablets.
This Part Includes Three Sections:
Section A: Introduction And Literature Review
This Section Includes An Introduction About The Pharmacological Actions Of Vildagliptin And Metformin, Their Chemical Structures, Physical Properties And Summary Of The Published Methods Developed For Their Analysis.
Section B: Determination Of Vildagliptin, Metformin, And Metformin Toxic Impurity (Melamine) By Mean Centering Of Ratio Spectra Spectrophotometric Method (MCR)
In This Section, Mean Centering Of Ratio Spectra Spectrophotometric Method (MCR) Has Been Developed And Validated For Quantitative Analysis Of VIL, MET, And MEL Using Methanol As A Solvent. The Amplitudes Of The Second Mean Centered Ratio Spectra At 218-218.2, 230.6, And 227.6-227.8 Nm Were Used For Determination Of VIL, MET And MEL, Respectively. Standard Spectra Of 10 µg/Ml VIL, 20 µg/Ml Of MET, And 0.6 µg/Ml MEL Were Used As Divisors. The Developed Method Specificity Was Assessed By The Analysis Of Different Synthetic Laboratory Prepared Mixtures And Good Results Were Obtained. Also, Accuracy Was Further Measured By Application Of Standard Addition Technique To Galvus Met® Tablets where No Interference from Additives Was Found.
Section C: Determination Of Vildagliptin, Metformin, And Metformin Toxic Impurity (Melamine) By Different chromatographic Methods
This Section Is Concerned With The Development Of Sensitive, Accurate And Specific TLC-Densitometric And HPLC Methods For Determination Of VIL, MET And MEL In Their Bulk Powder And Pharmaceutical Formulations. For TLC-Densitometric Method, Chloroform: Methanol: Formic Acid (4: 6: 0.3, By Volume) Was Used As A Developing System And 215 Nm As A Scanning Wavelength. While, For HPLC Method The Studied Components Were Well Separated Using Methanol : Acetonitrile : Mixture Of 0.01 M Sodium Dihydrogen Phosphate And 0.01 M Sodium Lauryl Sulphate (1:1), Ph=5 With Phosphoric Acid (35 : 25 : 40, By Volume) As The Mobile Phase Delivered At 1 Ml/Min Flow Rate. The Detection Was Performed At 205 Nm Using C18 Column. The Results Obtained Were Statistically Compared With The Reported One Using Student’s T-Test And Variance Ratio F-Test And No Significant Differences Were Obtained Regarding Both Precision And Accuracy.
This Thesis Contains 109 References, 46 Tables, 34 Figures, English And Arabic Abstracts.