الفهرس 
Part I: IntroductionOnly 14 pages are availabe for public view
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Abstract
In this thesis, synthetic somatostatin analogue OCT and a D2 receptor agonist ،BCT، were estimated using spectrophotometric, spectrofluorimetric methods in their authentic forms and dosage forms. Furthermore, OCT in combination with MID for HRS management were sparated and simultaneously determined with a validated TLC-densitometric method in authentic forms, dosage forms, human plasma, and urine. The thesis consists of six parts.
Part I: Introduction
This part provided an overview of the investigated drugs including their chemical structures, pharmacological usage, and reviews of previously published analytical approachesn for their determinations. Finally the goal of the proposed work was outlined.
Part II: Utilizing erythrosine B absorption spectral shifts for quantitative determination of octreotide and bromocriptine in their pure forms and pharmaceutical formulations.
OCT and BCT were quantified with a quick, simple, and sensitive spectrophotometric approach in their authentic forms and commercial dosage forms. This approach was based upon formation of ion pair complex between erythrosine B and investigated drugs in an aqueous buffered solution. For OCT determination the higher sensitivity was obtained using A at 525 (hypochromic shift). On the other hand, BCT was estimated using the absorbance at 556 nm (bathochromic shift). Under optimal conditions for the reaction, construction of calibration curves were performed within concentration range of 0.4 to 4 µg ml-1 for OCT and 1 to 9 µg ml-1 for BCT with with low detection limits of 0.094 and 0.235 µg ml-1 for OCT and BCT respectively.
Part III: Facile spectrofluorimetric approach based on native fluorescence for quantitation of octreotide in its pure form and pharmaceutical formulation; Evaluation of the method greenness.
This part presents the development and validation of a novel, rapid, highly sensitive, and relatively inexpensive spectrofluorimetric approach for the estimation of OCT in both its authentic form and pharmaceutical dosage form. The approach was dependant on monitoring OCT native fluorescence at an emission wavelength of 342 nm following excitation at 218 nm. Excellent linearity was achieved when constructing the calibration curve throughout the concentration range of 200–2000 ng ml-1. The LOD and LOQ values were found to be 55 and 169 ng ml-1, respectively. Avoiding interferencee with the dosage form’s excipients including lactic acid, mannitol, and sodium bicarbonate, the proposed approach was successfully used to assess OCT in its pharmaceutical ampoules. The developed method is easy to use and saves time. In addition, it avoids the need for expensive equipment, hazardous substances, or several steps of preparation for the sample. It may therefore be applied in quality control laboratories to detect and quantify OCT acetate.
Part IV: First spectrofluorimetric protocol for sensitive quantitative analysis of bromocriptine in pure form and pharmaceutical preparation, Evaluation of method greenness.
This part is focused on BCT determination using a spectrofluorimetric approach that is sensitive, accurate, fast, and cost-effective. The suggested approach relied on determination of BCT through mesuring its native fluorescence after improving its weak fluorescence by applying a micellar system of sodium dodecyl sulphate (2% w/v). The enhanced fluorescence intensity of BCT was monitored at 418 nm after excitation at 238 nm. By using a micellar system and adjusting the solution pH, the intensity of BCT fluorescence was increased approximately 15 times comparing to its native fluorescence. There was a linear relationship between the fluorescence intensity and BCT concentration in the range of (50 - 600 ng ml-1). The low LOD and LOQ values (15 and 44 ng ml-1, respectively) show that the method had a high degree of sensitivity. Without any excipient’s interference, the method was effectively employed to figure out BCT concentration in its pharmaceutical dosage forms.
Part V: Utilizing ninhydrine as a fluorescent probe for determination of octreotide acetate ̔ a synthetic peptide derivative ̕̕ in pure and its sandostatin ampules forms
This part is conceived to provide a novel spectrofluorimetric protocol for OCT determination in both its pure and dosage forms. The approach was evolved simply by condensing OCT with ninhydrin / phenyl acetaldehyde reagent in buffered media (pH 6.2). An intense fluorescence product was developed and its emission could be measured at 463 nm (after excitation at 390 nm). After optimization for different experimental parameters, the calibration curve could be constructed in a wide linear range (0.2 - 4.0 µg ml-1). The detection and quantitation limits were equal to 0.07 and 0.2 µg ml-1, respectively. Furthermore, the developed approach can potenially be used to quantitatively estimate OCT in its ampoules with great accuracy and precision.
Part VI: TLC method for separation and simultaneous quantitation of hepatorenal syndrome combination therapy “octreotide and midodrine”. application to pharmaceutical formulation, spiked human plasma and urine
In this part, the first TLC densitometric approach was evolved for separation and quantitative determination of OCT and MID. As a stationary phase, TLC silica gel 60 F254 plates was employed and methanol: methylene chloride: ammonia (8:2:0.2 v/v/v) as a mobile phase. The bands of the separated drugs were detecte at 218 and 300 nm with retardation factors (Rf) of 0.24 and 0.64 for OCT and MID, respectively. The Proposed method demonstrated a good linearity extent from 50 up to 1500 ng/spot for both drugs with high linearity (r=0.9999). The detection limits were 16 and 15 ng/spot for OCT and MID respectively. The method was applied for the drug analysis in their combined form either laboratory prepared mixture or pharmaceutical dosage forms. Furthermore, the developed approach could be effectively applied to spiked human plasma and urine
All approaches were assessed for linearity, accuracy, precision, limits of detection, and limits of quantitation in compliance with ICH validation recommendations. Additionally, the environmental friendliness of the investigated methods were assessed with some of the recent green analytial chemistry metrics.