الفهرس 
Part I: IntroductionOnly 14 pages are availabe for public view
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Abstract
The present thesis is focused on the development of the first spectrophotometric, HPLC, and spectrofluorometric methods for the simultaneous determination of new approved combinations containing three antihistaminic drugs, ALC, OLO, and BIL as well as an anti-inflammatory drug, KET. In addition, to set up the first spectrofluorimetric method for the determination of ALC and OLO as well as improving the spectrofluorimetric determination of BIL. The study is divided into four parts:
Part I: Introduction
This part includes a brief introduction to antihistamine, and anti-inflammatory drugs. It also includes; the physical and pharmacological characteristics of ALC, OLO, BIL, and KET. A summary of the reported analytical methods used for the determination of the mentioned drugs is also presented.
At the end of the introduction, the investigation scope of the thesis is outlined.
Part II: Spectrophotometric methods:
Chapter 1: Smart spectrophotometric methods based on feasible mathematical processing and classical chemometry for the simultaneous assay of Alcaftadine and Ketorolac in their recently approved pharmaceutical formulation.
In this chapter, three different chemometric method based on spectrophotometry were presented showing simplicity in their application. The investigated spectrophotometric chemometric methods include: first derivative, dual-wavelength, and iso-absorbance methods. These methods display good analytical performance concerning accuracy and precision. The measurements were carried out in 0.01 M NaOH as it gave the highest absorbance and fulfill all spectrophotometric and chemometric criteria. The proposed methods were successfully applied for the analysis of ALC and KET in laboratory prepared formulation that simulate the recently approved combined pharmaceutical formulation. The proposed methods were found to be time-saving, cheap, and easy. The proposed methods are the first methods for the analysis of the ALC and KET combinations in their pharmaceutical formulation.
Part III: chromatographic methods:
Chapter 1: High-Performance Liquid chromatography with Ultraviolet detection for the simultaneous determination of Alcaftadine and Ketorolac in their newly approved pharmaceutical formulation.
In this chapter, a sensitive, precise, and isocratic reversed-phase HPLC-UV method has been developed for the simultaneous determination of KET and ALC in pharmaceutical formulations. The mobile phase used for the separation was a mixture of phosphate buffer (10 mM, pH 3.0): methanol (20:80 v/v) with a flow rate of 1.0 mL/min. The retention times were found to be 2.5 and 4.4 min for ALC and KET, respectively. All measurements were carried out at 290 nm. Calibration curves were linear over the concentration ranges of 5-35 and 2-40 µgmL-1 for ALC and KET, respectively and the correlation coefficients (r) were higher than 0.999. The limits of detection (LOD) were 1.43 and 0.44 µg mL-1 while the limits of quantitation (LOQ) were 4.34 and 1.33 µg mL-1 for ALC, and KET, respectively.
The proposed method was successfully applied for the analysis of laboratory prepared formulation that simulate the recently approved pharmaceutical formulation containing ALC and KET combination.
Part IV: Spectrofluorimetric methods:
Chapter 1: The analysis of the antihistaminic drugs, Alcaftadine and Olopatadine, through facile ion-pairing with xanthine-based eosin Y as a spectroscopic probe.
In this chapter, the proposed method includes the use of eosin Y as an ion-pairing reagent to form a binary complex with ALC or OLO. The ion-pairing reaction was employed in two spectroscopic methods, fluorometric and colorimetric methods. The spectrofluorometric method was performed by monitoring the quenching effect of the drugs on the native fluorescence of eosin Y in acetate buffer (0.1 M, pH 3.8 for ALC) and (0.1 M, pH 3.3 for OLO) solution and the fluorescence quenching was measured at 540 nm after excitation at 302 nm for ALC and at 546 nm after excitation at 303 nm for OLO. The quenching effect was linear in a concentration range of 0.15 - 2.0 and 0.2 - 2.0 µg mL-1 for ALC and OLO, respectively. In the spectrophotometric method, the absorbance of the produced ion-pair complex was measured at 548 nm for ALC and at 546 nm for OLO in acetate buffer solution (0.1 M, pH 3.8 for ALC) and (0.1 M, pH 3.3 for OLO). Beer’s law was obeyed in the concentrations range of 0.8–8.0 and 1.0 - 1.0 µg mL-1 for ALC and OLO, respectively. The detection limits were 46.8 and 45 ng mL-1 in the spectrofluorimetric method and 0.214 and 0.209 µg mL-1 in the spectrophotometric method for ALC and OLO, respectively.
The presented methods were applied for the analysis of ALC and OLO in bulk and commercial pharmaceutical formulations. The proposed methodologies are time-saving, use minimal sample preparation steps and do not include tedious extraction procedures. In addition, the use of distilled water as a green solvent makes the proposed methods a good alternative to conventional methods that use harmful organic solvents. Moreover, the present work is considered the first spectrofluorometric methods that quantify ALC and OLO.
Chapter 2: Sensitive spectrofluorometric method for determination of Bilastine and its application to pharmaceutical preparations and biological samples.
In this chapter, a spectrofluorometric method has been developed for the analysis of BIL in bulk, commercial tablet formulation and human plasma. The suggested method was depending on the measurement of the native fluorescence of BIL in 1.0 M sulfuric acid at an emission wavelength of 385 nm after excitation at 272 nm. The relationship between BIL concentrations and the fluorescence intensities was linear in a range of 10.0–500.0 ng mL-1, and the correlation coefficient was 0.9999. The detection limit was 2.9 ng mL-1 and the quantitation limit was 8.8 ng mL-1.
The simple procedure of the method enabled its application in testing the tablet content uniformity. The suitable sensitivity and selectivity of the suggested method permitted its successful application for the analysis of BIL in real human plasma with appropriate recoveries (95.72% - 97.24%). In addition to simplicity, the proposed method is a time-saving that eliminates the tedious steps of sample preparation or extraction. The use of distilled water as a green solvent makes the proposed method a good alternative to conventional methods that use harmful organic solvents. Owing to its high sensitivity, the developed method was applied for BIL determination in real human plasma and the result was consistent with the previous studies.
Chapter 3: Sensitive synchronous spectrofluorometric method for determination of Montelukast Sodium and Bilastine; application to pharmaceutical preparations.
In this chapter, a very sensitive, first derivative synchronous spectrofluorometric method was developed for the simultaneous determination MTK and BIL. The method relied on measuring the synchronized fluorescence spectra of MTK and BIL at a fixed wavelength interval (Δλ) = 110 nm. The first derivates were derived and the peak amplitude at 381 and 324 nm were set for the determination of MTK and BIL, respectively. The effect of different factors on the studied drugs’ synchronized fluorescence spectra were investigated and adjusted. The calibration curves for both drugs were found to be linear over a concentration range of 0.05 -2.0 and 0.05 - 1.0 µg mL-1 for MTK and BIL, respectively. The LOD were found to be 17 and 11 ng mL-1 while The LOQ values were 50 and 33 ng mL-1 for MTK and BIL, respectively.
The proposed method was successfully applied to analyze MTK and BIL in their combined dosage form. The suggested method was also applied for the quantitative analysis of MTK and BIL in the spiked human plasma with no interference from the plasma matrix. The proposed method is a time-saving method because it uses simple sample preparation procedure and does not involve the use of organic solvent for extraction.
All analytical methods were validated according to ICH recommendations.
In addition, the thesis contains (40) tables, (36) figures, and (189) references, and English and Arabic Summaries.