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العنوان
Determination Of Certain Isomeric And Structureally Related Pharmaceutical Compounds Using Chemometrics /
المؤلف
ElMongy, Hatem Abdelfattah Mohamed.
هيئة الاعداد
باحث / Hatem Abdelfattah Mohamed Elmongy
مشرف / Abdel-Aziz El-Basyouni Mohamed Wahbi
مشرف / Ismail Ibrahim Ismail Hewala
مشرف / Marwa Said Hussein Moneeb
الموضوع
Pharmaceutical Analytical Chemistry.
تاريخ النشر
2013.
عدد الصفحات
149 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
العلوم الصيدلية
تاريخ الإجازة
1/1/2013
مكان الإجازة
جامعة الاسكندريه - كلية الصيدلة - Pharmaceutical Analytical Chemistry.
الفهرس
Only 14 pages are availabe for public view

from 148

from 148

Abstract

Part I :
This part contains is a general introduction to the isomeric compounds and the types of isomers (enantiomers, diastereomers and structural isomers) that have different pharmacological activity for the same drug. The introduction also includes the structurally related compound formed through isosteric replacements of functional groups and its effect on the pharmacological actions of drugs. The introduction illustrates the importance of studying the isomeric forms of drugs as more than 50 % of the world drugs are chiral or isomeric in general. The part is ended by enumerating the aim of the present research project.
Part II :
This part describes a novel chiral HPLC-DAD method for the determination of etodolac enantiomers in pharmaceutical formulations available in local market as tablets and soft gelatin capsules. The separation of the two enantiomers from racemic etodolac in tablets and capsules was carried out on Kromasil cellucoat chiral column. The study was extended to determine each enantiomer in human plasma aiming to study the pharmacokinetics of each enantiomer. The data of the pharmacokinetic parameters for each enantiomer was obtained from the chiral HPLC analysis of plasma samples obtained from three adult healthy volunteers after oral administration of etodolac tablet labeled to contain 300 mg of etodolac racemate. The drug enantiomers were extracted from the plasma samples using solid phase extraction technique on C18 cartridges. The proposed methods were validated according to USP analytical method validation elements and ICH guidelines and validation acceptance criteria were met in all cases.
Part III :
This part includes the application of the chemometric regression methods (PCR, PLS) for the simultaneous determination of ephedrine hydrochloride and its stereoisomer pseudoephedrine hydrochloride using the FT-IR spectroscopy. The methods were applied to the determination of the isomeric purity of these compounds in the pseudoephedrine hydrochloride raw material and for the determination of both compounds in their laboratories prepared mixtures. The method was validated using certain validation diagnostics which revealed that the method is accurate and precise with minimal errors of prediction in samples concentration.
Part IV :
This part includes the application of the chemometric regression methods (PCR, PLS) for the simultaneous determination of the positional isomers of cresol (ortho, meta, para) as the three isomers possess the same spectral features and the univariate spectral analysis is not
applicable duo to the extensive spectral overlap of these compounds. The methods were applied to the determination of the three isomers in laboratory prepared mixtures. The method was validated using certain validation diagnostics that showed that the method is accurate and precise with minimal errors of prediction in samples concentration.
Part V :
This part describes the application of an HPLC method to the separation and determination of the methylxanthines alkaloids i.e. caffeine, theophylline and theobromine in the presence of other biosynthesized structurally related compounds in the extracts of different brands of tea on reversed phase C18 column. The purity of separated peaks was tested by the application of the orthogonal functions (first, second) to the spectrochromatograms of the eluted peaks that were extracted at different time intervals across the peak. The ratios of the orthogonal functions (first, second) were calculated at the peak apices and compared to that of its standard compound. The characteristic features of a pure peak were described. The eluted peak due to theobromine was found to be impure due to the applied method in all investigated brands of tea so the method was developed to obtain pure peak of theobromine. The method was used to determine the contents of caffeine and theobromine in different extracts of tea while theophylline was not detected in any sample.
The developed method was validated according to USP analytical method validation elements and ICH guidelines and was shown to be specific, accurate, and of good precision.