الفهرس 
SummaryOnly 14 pages are availabe for public view
 |  | from | 299 |  |  |
| | | from | 299 | | |
Abstract
This Thesis Contains Three Separate Parts, Which Contain Different Analytical
Methods For Quantitative Determination Some Of Pharmaceutical Compounds
Containing Amine group Either In Their Pharmaceutical Formulations Or In Biological
Fluids.
Part I: Quantitative Determination Of Sofosbuvir, Paracetamol, And DL-
Methionine In Rat Plasma By Different chromatographic Methods With
Application To Pharmacokinetic Study
This Part Is Focused On Investigating Accurate, Sensitive, And Specific Methods
For Determination Of Sofosbuvir (SOF), Paracetamol (PAR), And DL- Methionine
(MET) In Rat Plasma By Two Different selective chromatographic Methods. These
Methods Were The First Developed Ones For Simultaneous Determination Of The Studied
Drugs In Rat Plasma With Their Application To Pharmacokinetic Study.
This Part Includes Three Sections:
Section A: Introduction And Literature Review
This Section Includes An Introduction About The Pharmacological Actions Of
Sofosbuvir (SOF), Paracetamol (PAR), And DL- Methionine (MET), Their Chemical
Structures, Physical Properties And Summary Of The Published Methods Developed
For Their Analysis.
Section B: Determination Of Sofosbuvir, Paracetamol, And DL- Methionine In
Rat Plasma Using Thin-Layer chromatography And Its Application To
Pharmacokinetic Study
In This Section, selective TLC-Densitometric Method Were Developed And Validated
Regarding To FDA Guidelines For The Simultaneous Analysis Of The Three Recommended
Drugs With A Developing System Consisted Of Chloroform: Methanol: Glacial Acetic
Acid: Formic Acid In The Ratio Of (9.5: 1: 1.5: 0.5, By Volume). The Studied Analytes
And The Internal Standard (Naphazoline Hydrochloride) Were Scanned At Wavelength
210 Nm. The Method Showed Linearity In The Concentration Range Of 160- 3000
Ng/Band For Sofosbuvir And Paracetamol, 300- 3000 Ng/Band For DL- Methionine.
Furthermore, Application Of The Developed Method Has Been Extended To In Vivo
Analysis In Rat Plasma. In Addition, Pharmacokinetic Behaviors Of These Drugs Have
Been Studied.
Section C: Determination Of Sofosbuvir, Paracetamol, And DL- Methionine In
Rat Plasma Using High Performance Liquid chromatography And Its
Application To Pharmacokinetic Study
In This Section, Rapid And Sensitive HPLC Method Has Been Developed And
Validated For Simultaneous Determination Of Sofosbuvir In Rat Plasma With Two Co-
Administered Drugs, Paracetamol And DL- Methionine Depended On Using HPLC
Method Whereas The Analytes And The Internal Standard (Cinnarizine) Were Separated
On An Xterra® HPLC RP C18 Column (250 × 4.6 Mm, 5µm) Using Gradient Mode
With A Mobile Phase Consisted Of Methanol And 0.1% Aqueous Triethylamine (TEA)
At Ph 3 Adjusted With Orthophosphoric Acid. The UV Detection Was Carried Out At
Wavelength 210 Nm. The Method Was Linear And Validated Over A Concentration Range
Of 150- 5000 Ng Ml-1 For Sofosbuvir, 300- 5000 Ng Ml-1 For Both Paracetamol And
DL- Methionine. All Validation Parameters Met The Acceptance Criteria According To
FDA Guidelines. The Developed Method Was Successfully Applied To A
Pharmacokinetic Study Of Sofosbuvir, Paracetamol, And DL- Methionine In Rats And
The Results Suggested The Availability Of Co- Administration Of These Drugs Without
Any Significant Effect On Their Pharmacokinetic Properties.
Part II: Stability Study Of Benztropine Mesylate Using Different Analytical
Methods
This Part Is Focused On Developing Simple, Accurate, Sensitive, And selective
Spectrophotometric And chromatographic Stability- Indicating Methods For
Determination Of Benztropine Mesylate (BNZ) And Its Hepatotoxic And Carcinogenic
Degradation Product; Benzophenone (BPH) In Pure Form And In Pharmaceutical
Formulation. The Most Important Advantage Of This Work Is That The Developed
Methods Are The First Developed Ones For Determination Of BNZ And Its Carcinogenic
Degradation Product.
This Part Includes Four Sections:
Section A: Introduction And Stability Study Of Benztropine Mesylate
This Section Includes An Introduction About The Pharmacological Actions Of
Benztropine Mesylate (BNZ), Its Chemical Structure And Physical Properties. Also,
It Is Includes Results Of Stability Study Of BNZ, Preparation Of Degradation Product
And Summary Of The Published Methods Developed For Analysis Of BNZ.
Section B: Stability Indicating Spectrophotometric Methods For Determination
Of Benztropine Mesylate And Its Carcinogenic Degradation Product
In This Section, Three Simple, Accurate, Sensitive, And selective Spectrophotometric
Stability- Indicating Methods For Determination Of Benztropine Mesylate (BNZ) And
Its Hepatotoxic And Carcinogenic Degradation Product; Benzophenone (BPH); Were
Developed And Validated. The Developed Spectrophotometric Methods Are; First
Derivative, First Derivative Of Ratio Spectra And Ratio Difference Methods.
Calibration Curves Of These Methods Are Linear Over The Concentration Ranges Of
5- 40 And 1- 20 Μg Ml-1 For BNZ And BPH, Respectively. Method (I); First Derivative
Spectrophotometric One where BNZ Was Measured At 228.2 Nm While BPH Was
Measured At 244 Nm. Method (II); First Derivative Of Ratio Spectra Spectrophotometric
One where The Overlapping Spectra Of BNZ And BPH Were Well Resolved And BNZ
Was Measured At 228.8 Nm While BPH Was Measured At 211 Nm. Method (III);
Ratio Difference Spectrophotometric Method Which Depended On Measuring The Ratio
Difference Between 214 And 224 Nm For Determination Of BNZ And At 227.5 And
237.5 Nm For BPH. These Methods Were Validated According To ICH Guidelines.
Section C: Stability Indicating TLC- Densitometric Method For Determination
Of Benztropine Mesylate And Its Carcinogenic Degradation Product
In This Section, An Accurate, Precise And Highly selective Stability Indicating
TLC- Densitometric Method Was Adopted For Simultaneous Determination Of
Benztropine Mesylate (BNZ) In Presence Of Its Hepatotoxic And Carcinogenic
Degradation Product, Benzophenone (BPH). The Method Depended On Separation Of
BNZ from Its Degradate On TLC Aluminum Plates Precoated With Silica Gel 60 F254
As The Stationary Phase Using A Developing System Consisted Of Hexane: Methylene
Chloride: Triethylamine (50: 50: 6, By Volume) And Scanning The Separated Bands At
235 Nm. The Method Was Successfully Applied To Available Marketed Dosage Form
where No Interference from Excipients Was Found.
Section D: Stability Indicating UPLC Method For Determination Of
Benztropine Mesylate And Its Carcinogenic Degradation Product
In This Section, A selective, Sensitive, And Fast Ultra-Performance Liquid
Chromatographic (UPLC) Method Was Developed And Validated To Determine BNZ
And Its Oxidative Degradate (BPH) At Which The Mixture Was Separated On A Reversed
Phase C8 Analytical Column (50 × 2.1 Mm, 1.9 µm) Using A Mobile Phase Of
Acetonitrile: Aqueous Sodium Dodecyl Sulfate (SDS) (50: 50, V/V) Adjusted To Ph =3
With Phosphoric Acid, At A Flow Rate Of 0.5 Ml Min-1. Quantification Was Achieved At
210 Nm Based On Peak Area And Linear Calibration Curves Over Concentration Ranges
Of (2- 200 Μg Ml-1) And (0.5- 50 Μg Ml-1) For BNZ And BPH, Respectively, Were
Obtained. The Investigated Method Were Successfully Applied To Dosage Form And
Method Validation Has Been Carried Out. The Results Obtained By Applying This Method
Were Analyzed And Compared With Reported One And No Significant Difference Was
Obtained Regarding Both Accuracy And Precision.
Part III: Quantitative Determination Of Clotrimazole And Hydrocortisone By
Different Analytical Methods
This Part Is Focused On Investigating Simple And Accurate Spectrophotometric And
Chromatographic Methods For The Determination Of Clotrimazole (CLO) And
Hydrocortisone (HDC) In Their Pure Form And In Their Combined Formulation. The
Developed Spectrophotometric And chromatographic (UPLC) Methods Were Applied
For Determination Of CLO And HDC In The Topical Cream With High selectivity And
Sensitivity.
This Part Includes Four Sections:
Section A: Introduction And Literature Review
This Section Includes An Introduction About The Pharmacological Actions Of
Clotrimazole (CLO) And Hydrocortisone (HDC), Their Chemical Structures, Physical
Properties And Summary Of The Published Methods Developed For Their Analysis
In Their Single Forms And In Their Binary Mixture.
Section B: Quantitative Determination Of Clotrimazole And Hydrocortisone
By Different Spectrophotometric Methods Manipulating Ratio Spectra
In This Section, Different Precise, Accurate, And selective Three Spectrophotometric
Methods Have Been Developed And Validated For The Determination Of Clotrimazole
(CLO) And Hydrocortisone (HDC) In Their Combined Dosage Form. The Developed
Spectrophotometric Methods Were First Derivative Spectrophotometry (1D),
The Second Derivative Of Ratio Spectra (2DD), And Mean Centering Of Ratio Spectra
(MCR) Spectrophotometric Methods. All These Methods Were Tested By Their
Application For Determination Of The Studied Drugs In Pure Forms And Laboratory
Prepared Mixtures And No Interference from Any Of Them On Determination Of The
Other Was Found. Methods Were Then Validated And Applied To Pharmaceutical Dosage
Form.
Section C: Quantitative Determination Of Clotrimazole And Hydrocortisone
By Different Spectrophotometric Methods Manipulating Absorbance
Difference
In This Section, Two Accurate, Sensitive, And selective Spectrophotometric
Methods Have Been Developed For The Determination Of Clotrimazole (CLO) And
Hydrocortisone (HDC) In Their Combined Dosage Form. The Developed Methods Were
Dual Wavelength (DW) Method where CLO Was Determined Using The Absorbance
Difference Between 225.4 And 264 Nm, While HDC Was Determined Using The
Absorbance Difference Between 228 And 247 Nm. The Second Method Was Advanced
Absorbance Subtraction (AAS) Method At Which A Unified Regression Equation Was
Constructed Using The Absorbance At ʎiso = 225.4 Nm And Used For Calculating
Concentrations Of CLO And HDC In The Binary Mixture After Simple Mathematical
Calculations. Methods Validation Were Carried Out Regarding Linearity, Accuracy,
Precision, And selectivity And They Were Found To Be Suitable For Quality Control
Analysis Of The Studied Drugs.
Section D: Quantitative Determination Of Clotrimazole And Hydrocortisone
By UPLC Method
In This Section, A Sensitive, And Fast Analytical Method For Simultaneous
Quantitative Determination Of Clotrimazole (CLO) And Hydrocortisone (HDC) Was
Developed And Validated By Using UPLC Method. The Mixture Was Separated On
Hypersil Gold C18 Column (150 × 4.6 Mm, 3 µm) Using An Isocratic Method With
Mobile Phase Consisted Of Acetonitrile: Water (50: 50, V/V), At A Flow Rate Of 1 Ml
Min-1 At Room Temperature With Analysis Time Of Less Than 2.5 Min. The Drugs Were
Detected At 228 Nm Over A Concentration Range Of (5- 35 Μg Ml-1) And (5- 50 Μg
Ml-1) For CLO And HDC, Respectively. The Proposed Method Have Been Successfully
Applied For Determination Of CLO And HDC In Bulk And In Their Pharmaceutical
Formulations. The Results Obtained Were Statistically Analyzed And Compared With
The Reported One Using F And Student’s T-Tests And No Significant Differences Were
Obtained Regarding Both Accuracy And Precision.