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العنوان
Determination of some angiotensin converting enzyme inhibitors in drug formulations and biological fluids /
المؤلف
El-sebaei, Fawzi Abd alla.
هيئة الاعداد
باحث / Fawzi Abd alla El-sebaei
مشرف / Zhu Yan
باحث / Fawzi Abd alla El-sebaei
مناقش / Zhu Yan
الموضوع
Pharmaceutical. HPLC. Chromatography.
تاريخ النشر
2011.
عدد الصفحات
203 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Analytical Chemistry
تاريخ الإجازة
15/12/2011
مكان الإجازة
جامعة المنصورة - كلية الصيدلة - Department Of Analytical Chemistry
الفهرس
Only 14 pages are availabe for public view

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from 203

Abstract

This thesis is devoted to develop new simple analytical procedures for the determination of seven pharmaceutically important drugs belonging to the group of Angiotensin Converting Enzyme inhibitors; namely, benazepril HCl (BZL), enalapril maleate (ENP), fosinopril sodium (FSP), lisinopril (LSP) and ramipril (RMP) and two metabolites captopril disulfide (CPD) and enalaprilat (ENT) together with hydrochlorothiazide (HCT). The drugs are nowadays massively administrated due to their efficacy. The developed methods have been applied for the determination of such class of drugs in their raw materials and pharmaceutical tablets as well as in spiked human plasma and urine. The thesis comprises four main parts:
Part I: This part represents a general introduction about the studied drugs, their uses, adverse effects, chemical properties, mode of action, and pharmacological effects as well as a literature review about the published analytical procedures for their analysis.
Part II: In this part, the development of a reversed phase liquid chromatographic method for the simultaneous determination of 7 ACE inhibitors together with the mostly concurrent administrated drug hydrochlorothiazide in pharmaceutical formulations as well as spiked human plasma and urine is described. The method utilizes a simple gradient procedure for the separation in an 11-min run time using acetonitrile aqueous ammonia buffer (pH 9) solution and an Extend RP-C18 (25 μm particle size, 4.6 x 250 mm, Agilent) HPLC column.
Part III: In this part, a simple and highly selective method for determination of benazepril hydrochloride (BZP), enalaprilat (ENT) and lisinopril (LSP) in pharmaceutical dosage forms as well as spiked human plasma by ion chromatography with UV detection has been developed. The method proposed is based upon ionization of those two drugs in basic medium to be well retained and readily resolved as dicarboxylic acid anions using IonPac AS11. The fundamental advantage for the procedure lies in its ability to enhance drugs retention allowing a confident analysis in complex matrix.
Part IV: Angiotensin Converting Enzyme (ACE) inhibitors peak profile in liquid chromatography usually suffer more or less peak deformation and even splitting. This phenomenon leads in most cases to misidentification and inaccurate determination of the peaks. This is attributed to the cis-trans interconversion phenomenon. In this paper, SCS1 analytical column was tried for analysis of the selected compounds. This leads to much improvement of their peak profiles which permits their analysis at normal temperature and ordinary pH. The developed procedure was applied for simultaneous analysis of the studied drugs in their tablets and human plasma with satisfactory results.
Part V: A simple method for the simultaneous determination of five Angiotensin Converting Enzyme inhibitors namely benazepril HCl (BZL), enalapril maleate (ENP), enalaprilat (ENT), lisinopril (LSP) and ramipril (RMP) using ion chromatography (IC) with direct conductivity detection (CD) based on their ionization in acidic medium without chemical suppression is presented. A commercial ion chromatograph as sole equipment can be used for routine analysis of this pharmaceutically widely administrated drug class without any modification.