الفهرس 
Part I: Introduction
General introductionOnly 14 pages are availabe for public view
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Abstract
In the present thesis, two drugs that are used for management of hypotension namely HTM and MDR were estimated using different spectrofluorimetric approaches in addition to one TLC densitometric method. This thesis is consisted of three parts:
Part I: General introduction
This part provides general information about the studied drugs such chemical structure, nomenclature, solubility, therapeutic uses and literature review of reported methods for analysis of these drugs in pure forms, pharmaceutical preparations and biological fluids. This part ends with the scope of investigation of the present study.
Part II: Spectrofluorimetric methods
This part consists of three chapters
Chapter 1: Spectrofluorimetric Investigation of the interaction between midodrine and sodium dodecyl sulfate and its utility for midodrine determination in pharmaceutical dosage forms and Content uniformity testing
A new, straightforward spectrofluorimetric approach with high sensitivity was established for determining MDR hydrochloride based on enhancement of MDR native fluorescence by addition of sodium dodecyl sulfate surfactant above its critical micelle concentration in presence of Torell & Stenhagen buffer (pH 6.0). The fluorescence was measured at 324 nm after being excited at 291 nm. Results show that the proposed method is highly sensitive with high linearity ranging from 0.025 to 3 µg mL-1. The lower limits of detection and quantification were 9.8 and 30 ng.mL-1, in the respective order. The proposed approach was analytically assessed through applying the ICH guiding rules. The suggested approach was effectively utilized for estimation of the medicine in its market tablet formulations with excellent recovery and without any interfering effect from excipients. The presented approach was moreover utilized to test the uniformity of commercial tablets contents following the guidelines of the USP.
Chapter 2: Spectrofluorimetric approach for determination of heptaminol and midodrine in pharmaceutical formulations and human plasma using OPA as a fluorescent probe.
The antihypotensive drugs; HTM and MDR were determined by spectrofluorimetric method using ortho-phthaldehyde as a fluorescence probe. These drugs were condensed with the reagent in the presence of 2-mercapto-ethanol. The reaction was carried out in slightly alkaline aqueous solution containing 0.1 M sodium hydroxide for HTM or buffered medium using 0.1 M borate buffer (pH 9.0) for MDR. The resulting products exhibited high fluorescence activity that were measured at 451 or 441 nm after excitation at 334 or 335 nm for HTM and MDR, respectively. The linearity range of the method was 5 - 100 ng mL-1 and 0.1-1.5 µg.mL-1 with a lower detection limit of 1.8 and 31 ng ml-1 for HTM and MDR, respectively. The procedure was analytically evaluated according to the International Council of Harmonization. The proposed method was applied to analyze the cited drugs in pharmaceutical tablets and oral drops. In addition, the present study represents the first spectrofluorimetric method for the determination of HTM in real human plasma without any interference from the components of the human plasma. The method also was applied for testing the content uniformity of commercial tablets formulation of MDR.
Chapter 3: Utility of dansyl chloride for establishment of a sensitive spectrofluorimetric approach for estimating heptaminol hydrochloride and midodrine hydrochloride.
A highly sensitive spectrofluorimetric approach was established for determining HTM and MDR through derivatization with 1-dimethylaminonaphthalne-5-sulphonyl (Dansyl chloride). The resulting fluorescent product was extracted with methylene chloride followed by measuring the emission at 490 or 532 nm after being excited at 345 or 339 nm for HTM and MDR respectively. The reaction was proceeded in aqueous medium buffered with 0.1 M borate buffer (pH 10.5 or 8.2 for HTM and MDR). The proposed method exhibited high linearity in drug concentrations ranging from 0.03 to 2.0 µg mL-1 for HTM and 0.1 to 3.0 µg mL-1 for MDR. The lower limits of detection and quantification were 16 and 48 ng.mL-1 for HTM while for MDR the values were 29 and 88 ng mL-1. Analytical performance of the proposed approach was assessed through applying the ICH guiding rules. The suggested approach was effectively utilized for the analysis of the commercial pharmaceutical formulation (tablet and oral drops) containing the investigated drugs with excellent recovery and without any interfering effect from excipients.
Part III: chromatographic method
Studying the kinetic of midodrine degradations using TLC Stability indicating approach: Application to dosage form and human plasma
A simple, rapid and selective thin layer chromatographic method has been developed for estimation of the antihypotension drug, MDR hydrochloride, in pure form, tablet, spiked plasma and stress degraded samples. Separation was carried out using silica gel 60-F254 as a stationary and mobile phase consisting of methanol: methylene chloride: ammonia in ratio of 8:2:0.2 (by volume).The detection was carried out in the absorbance reflectance mode at wavelength of 290 nm. The retardation factor was found to be 0.7 and 0.49 for MDR and its main degradation product, DG-MDR. The method showed linearity for MDR over a concentration range of 50-1500 ng/spot with good correlation and determination coefficient. The method was applied successfully for the analysis of commercial tablets and oral drops with good recovery and without interference of their excipients. The method was also applied for studying the stability of the cited drug under different stress conditions including acidic, alkaline, hydrolytic, oxidative and photo- degradations. Results demonstrated the liability of the drug to hydrolysis with acid and alkali while neutral hydrolysis, oxidation, and photolytic stress conditions did not affect the drug stability. Furthermore, the kinetic of acidic and alkaline degradations was investigated and the rate constants were found to be 0.620 and 0.074 K h−1 while half life time (t1/2) values were 1.12 and 9.32 h, respectively. All proposed methods were summarized.