الفهرس 
Part I: IntroductionOnly 14 pages are availabe for public view
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Abstract
The presented thesis is concerned with the development of new and sensitive methods with simple procedure for the analysis of some non – sedating antihistamines (NSAs) namely; LORA, FEXO and CET. In addition, combination of montlukast with some antihistamines shows synergistic effect therefore there is great need to develop sensitive method for simultaneous determination of Montlukast with the previously mentioned antihistamine.
The thesis comprises four main parts.
Part I: Introduction
This part includes general introduction about antihistamines especially NSAs, their classification, medicinal importance, chemistry, mechanism of action, and pharmacokinetics in addition to a literature review including the official and reported (non-official) methods for their determination. At the end of the introduction part, the aim of the thesis is illustrated.
Part II: chromatographic methods:
This part is comprised of three chapters:
Chapter I: Concurrent estimation of montlukast and loratadine mixture in spiked human plasma utilizing HPTLC with UV detection.
In this chapter, a novel, fast, and cost-effective high performance thin layer chromatography (HPTLC) with reflectance/absorbance mode was developed and validated for simultaneous estimation of MONT and LORA. Separation was attained on pre-coated silica gel TLC plate with chloroform: ethyl acetate (8:2 v/v) as a mobile phase. Quantification was performed at 280 nm in range concentrations of 48-300 ng/band for MONT and 90-600 ng/band for LORA. The developed methodology was validated on the basis of the International Council on Harmonization (ICH) guidelines. The proposed TLC system gave compact bands with high resolution at retardation factor (Rf) of 0.17 ± 0.002 for MONT and at 0.39 ± 0.001 for LORA. The lower detectable amounts were 9.5 and 22.2 ng/band, and the limits of quantitation were 28.7 and 67.2 ng/band for MONT and LORA respectively. The method could efficiently be utilized for the detection and estimation of MONT and LOR simultaneously in pure powders and in plasma samples of human.
Chapter 2: Ultrasensitive TLC determination of montlukast and loratadine mixture in human plasma utilizing fluorescence detection at dual pH values: Toward attaining maximum fluorescence intensity.
In this chapter, a novel selective and highly sensitive TLC method with reflectance/fluorescence detection was developed to separate and quantify MONT and LORA. Separation of the studied drugs was performed on precoated silica gel TLC plates using chloroform: ethyl acetate (8 :2 v/v) as a mobile phase. MONT quantification was carried out by measuring emission using 400 nm optical filter after excitation at 340 nm. Enhancement of the week LORA fluorescence was performed through adequate spraying the chromatograms with 0.2 M perchloric acid. The scanner was set at 275 nm excitation wavelength and 400 nm optical filter. The linear regression analysis data of the studied drugs showed a good linear relationship with correlation coefficients of 0.9987 for MONT and 0.9984 for LORA over the concentration range of 6 – 100 ng/band for MONT and 15 – 120 ng/band for LORA. Limit of detection values were 1.6 and 4.5 ng/band, and the limits of quantitation were 4.7 and 13.8 ng/band for MONT and LORA respectively. The analytical performance of the proposed method was evaluated according to the International Council for Harmonization (ICH). The method was successfully applied for the simultaneous analysis of the studied drugs in spiked human plasma and good recovery percentages were obtained indicating that there is no interference from plasma constituents. Therefore, the method can be applied for in vivo analysis and pharmacokinetic study.
Chapter 3: Fluorescence thin-layer chromatography determination of loratadine and montlukast in bulk drug and spiked human plasma.
In this chapter, for the accurate and precise quantification of LORA and MONT, new sensitive, simple, and fast, TLC techniques were developed and verified for each drug separately. The TLC method was carried out on an aluminum plates precoated with silica gel 60 F254 with chloroform: ethyl acetate (8:2 v/v) as a mobile phase for LORA and ethyl acetate: ethanol: ammonia (6: 2.5: 1.5 v/v/v) for MONT. For the first time, the detection mode of reflectance/fluorescence was used. Because, the native fluorescence of LORA was very weak, so low sensitivity was obtained. However, spraying the chromatogram with 0.2 M perchloric acid boosted the intensity of the weak LORA. LORA was scanned using a 275 nm excitation wavelength and a 400 nm optical filter. For MONT quantification, the emitted light was measured using 400 nm optical filter after excitation at 340 nm directly without spraying with perchloric acid because MONT has strong fluorescence owing to its highly conjugated system. The Rf values were 0.32 ± 0.001 and 0.64 ± 0.001 for LORA and MONT, respectively.
Based on the International Conference on Harmonization (ICH) criteria, the approaches were tested for linearity, range, accuracy, intermediate precision, repeatability, and robustness. In range of concentrations 6–120 and 3 – 150 ng/band, the proposed techniques indicated satisfactory linear relationship with correlation values of 0.9995 and 0.9991 for LORA and MONT, respectively. The least detectable levels were determined to be 1.88 ng/band for LORA and 0.89 ng/band for MONT, while the quantitation limits were found to be 5.71 ng/band for LORA and 2.69 ng/band for MONT. The approaches were successfully used to determine LORA and MONT in both bulk drug, pharmaceutical tablets and plasma samples.
Part III: Flow injection analysis
This part is comprised of one chapter:
Part III: Ultra-sensitive determination of some anti-histaminic drugs by flow injection analysis utilizing native and micelle-enhanced fluorescence detection in spiked human urine
In this chapter, highly sensitive, rapid, and simple two flow injection analysis methods have been developed and validated to determine LORA and CET. The first method is based on measuring the native fluorescent signals at 455 nm after excitation at 279 nm for LORA and at 294 nm after excitation at 235 nm for CET. The peak area – concentration plots of LORA and CET were linear over the concentration ranges of 20 – 5000 and 50 – 2000 ng/ml, respectively, with correlation coefficients (r) of 0.9989 and 0.9996 for LORA and CET, respectively. The calculated LOD and LOQ were 6.2 and 18.9 ng/ml for LORA and 16.0 and 48.4 ng/ml for CET, respectively. The second method is based on an improvement of the fluorescence behavior of the studied drugs in the presence of 1.44 % w/v sodium dodecyl sulfate (SDS). The presence of the micellar system achieved about 4.4 and 3.6-folds enhancement in the relative fluorescent signals for LORA and CET, respectively. The peak area – concentration plots using 1.44 % w/v SDS micellar system were linear over the concentration ranges of 5 – 4000 and 30 – 3000 ng / ml with correlation coefficients (r) of 0.9981 and 0.9976 for LORA and CET, respectively. The calculated LOD and LOQ values in micellar media were 1.4 and 4.2 ng/ml, respectively for LORA and 4.5 and 13.6 ng/ml respectively for CET, respectively, which indicate the high sensitivity of the proposed method. The proposed methods were validated according to ICH guidelines and have been successfully applied in the analysis of these drugs in spiked human urine with acceptable values of recovery percentages (96.39 – 101.49 %) ± (1.37 – 2.13, n = 6) for LORA and (95.28 – 102.08) ± (1.38 – 2.17, n = 6) for CET.
Part IV: Spectrofluorimetric methods
This part is comprised of one chapter:
Part IV: Micelle‐enhanced specific spectrofluorimetric determination of Fexofenadine in tablets and human plasma.
In this chapter, a simple, green and specific spectrofluorimetric method for direct determination of FEXO was developed and validated. The proposed method depends on micelle enhancement of the native fluorescence of FEXO via sodium dodecyl sulfate (SDS) as miceller media. Upon using 0.5 % w/v SDS as miceller system; about 2.3 folds enhancement in the fluorescence intensity of FEXO was attained compared to aqueous system, which was measured at 295 nm after excitation at 221 nm. A correlation coefficient of 0.9997 was obtained for the relationship between the fluorescence intensity and drug concentration in a range of 0.01 – 2 µg/mL. The limits of detection and quantification were 3.2 and 9.7 ng/mL, respectively, Worthwhile, the high sensitivity and specificity of the developed method permits its application for the analysis of the studied drug in pharmaceutical dosage form and spiked human plasma with good % recovery without any interference from tablet excipients and plasma matrices. The method has acceptable accuracy and precision which were revealed through comparison with the reported method using Student’s t-test and Fisher’s variance test.
In addition, the thesis included a summary in English and another in Arabic. The thesis is composed of 182 pages and included 33 figures, 41 tables and 293 references arranged according to their appearance in the thesis.