الفهرس 
Part I: General introductionOnly 14 pages are availabe for public view
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Abstract
The present thesis is devoted to the development and validation of cost-effective and environmentally safe analytical methods for the determination of some centrally acting drugs namely; asenapine maleate, dapoxetine hydrochloride, milnacipran, baclofen, and duloxetine hydrochloride. The developed methods include spectrofluorimetric, spectrophotometric, resonance Rayleigh scattering, and FTIR spectroscopic techniques.
The presented thesis falls into two main parts:
Part I: General introduction
This part provides an overview of the pharmaceutical importance, pharmacological effect, mechanism of action, and chemical structure of the studied drugs. It also includes the analytical review for the analytical techniques that were previously reported for the determination of the studied drugs in pure forms, dosage forms, and biological fluids. At the end of this part, the objective of the suggested work was outlined.
Part II: Spectroscopic techniques
This part falls into eight chapters:
Chapter I: One-pot reaction for determination of Asenapine maleate through facile complex formation with xanthene based dye; Application to content uniformity test
In this chapter, two spectroscopic methods were developed and validated for sensitive and rapid determination of asenapine. Both methods depend on the association complex formation between xanthene-based dye (eosin Y) and the cited drug in acetate buffer (pH=3.8). In the spectrophotometric method (method I), the absorbance of the formed complex was estimated at maximum wavelength of 545 nm and Beer’s law was obeyed in the range of 1 – 12 µg mL-1. The spectrofluorimetric method (method II) depends on measuring the quenching effect of the drug on the native fluorescence of eosin Y at 545 nm after excitation at 303 nm. The linearity range of method II was 0.4 – 3.2 µg mL-1. The limits of detection were 0.24 and 0.08 µg mL-1 for the method I and II, respectively. The instructions of ICH were followed to fully validate the developed analytical procedures. The formation constant of the formed complex was 3.93×104 while Gibb’s free energy was -2.6×104 J mol-1. Finally, the methods were applied for the analysis of pharmaceutical tablets and the evaluation of their content uniformity.
Chapter 2: One-pot micellar augmented native fluorescence for facile fluorimetric assay of dapoxetine hydrochloride in biological plasma and tablets
This chapter was devoted to the development of an innovative, non-extractive, environmentally safe protocol for the assay of dapoxetine in biological plasma and tablets. The phenomenon of the assay is simple and only based on native fluorescence which is enhanced by the addition of micelle. Variables that affect the method were optimized and measurements were accomplished in SDS micellar medium at emission wavelength 338 nm after excitation at 294 nm. The fluorescence-concentration plot was rectilinear over the range (0.1 – 4 µg mL-1 ). Directives of ICH guidelines were followed to ensure the validity of the procedure. The limit of quantitation and detection were 0.098 and 0.03 μg/ml. the procedure was utilized in the dosage form analysis and statistical comparison with the reported method revealed excellent accuracy and precision of the proposed method. Finally, the method was extended to include biological plasma analysis, with good percentage recovery.
Chapter 3: A new approach based on isoindole formation reaction for sensitive fluorimetric assay of milnacipran in tablets and biological fluids (plasma/ urine)
The chapter describes a new, sensitive, and economic protocol for milnacipran analysis. In the presence of 2-mercaptoethanol, the amino moiety of milnacipran condenses with o-phthalaldehyde to generate isoindole fluorescent derivative. The isoindole product was measured at (λex 338.5 nm, λem 433.5 nm) and reaction variables were investigated and optimized. The fluorescence intensity of measurements was plotted versus milnacipran concentration to give a linearity range over 200 – 4000 ng/mL. The proposed approach was fully validated by the directives of ICH guidelines and applied without any influence of the combined excipient for milnacipran tablet analysis. Furthermore, the procedure was applied in spiked urine and plasma analysis with excellent percentage recovery.
Chapter 4: A new convenient methodology based on dihydropyridine derivative for selective fluorimetric analysis of baclofen: Application to spiked urine and content uniformity evaluation
In this chapter, a new, convenient, and selective fluorimetric method for baclofen determination has been developed. The analytical methodology depends on Hantzsch reaction that leads to formation of dihydropyridine fluorescent derivative. The primary amino moiety in baclofen was condensed with two equivalents of acetylacetone in the presence of formaldehyde and acetate buffer solutions. Spectrofluorimetric monitoring of the product was accomplished at emission wavelength 477.3 nm after excitation at 419.9 nm. The method exhibited linearity between baclofen concentration and the fluorescence intensity in the range of 0.3 – 6 µg/mL. Adjustment of the reaction variables and studying validation parameters according to directives of ICH were performed. Ultimately, the proposed approach was applied successfully for baclofen determination in raw material, dosage form, and spiked human urine and extended to test content uniformity of baclofen tablet.
Chapter 5: A new feasible approach based on utility of ninhydrin for selective fluorimetric analysis of baclofen. Application to content uniformity evaluation
The attention in this chapter was directed to developing a new, feasible, and selective fluorimetric approach for baclofen determination. The analytical approach relies on the utility of ninhydrin for the formation of fluorescent derivative that was monitored at (λex 386 nm, λem 480 nm). At suitable reaction conditions, the primary amino moiety in baclofen is condensed with ninhydrin and phenylacetaldehyde in the presence of Teorel buffer as a buffered medium. The method exhibited linearity between baclofen concentration and fluorescence strength in the range of 1 – 10 µg mL-1. The limit of quantitation and detection were 0.68 and 0.22 μg/ml. Adjustment of the reaction variables and evaluating the validation parameters according to directives of ICH were performed. Moreover, an interference study was implemented to ensure that no discrepancy from the excipient on the result of the analysis. Finally, the proposed method was applied successfully for baclofen assay in dosage form and extended to test Mylobac content uniformity.
Chapter 6: Two facile approaches (spectrofluorimetric, resonance Rayleigh scattering) based on association complex with Erythrosine-B for Nano-level analysis of duloxetine. Application to content uniformity
In this chapter, two facile, sensitive, and eco-friendly methods were implemented for duloxetine analysis. Both methods rely on the binary association complex between Erythrosine-B and duloxetine in an acidic medium. While spectrofluorimetric simply utilizes the quenching action of DLX on the native fluorescence of erythrosine at emission 557.2 nm (λex = 528.6), the resonance Rayleigh scattering depends on measurements of the augmentation of resonance Rayleigh scattering of Erythrosine-B spectrum due to DLX addition at 357.2 nm. All variables affecting the complex formation were studied and precisely optimized. The validated approaches provide linearity between response and duloxetine concentration over 100 – 2400 ng mL-1 and 200 – 2000 ng mL-1 for spectrofluorimetric and RRS methods, respectively. The criteria of validation were performed by the recommendation provided by ICH. The values of LOD were 30 and 56 ng mL-1 for spectrofluorimetric and RRS methods, respectively. Finally, both approaches were applied with acceptable results for pharmaceutical formulation analysis and evaluation of cympatex capsules content uniformity.
Chapter 7: Investigation of the association complex formed between dapoxetine and erythrosine-B for facile dapoxetine assay in pharmaceutical formulation using resonance Rayleigh scattering and spectrofluorimetric techniques
Herein, two facile, sensitive, and green compatible approaches were established for dapoxetine assay. The approaches chemically rely on association complex formed between erythrosine-B and dapoxetine in an acidic buffered medium. The quenching impact of the formed complex on the native erythrosine fluorescence at emission 553.5 nm is simply the main idea of spectrofluorimetric assay while resonance Rayleigh scattering methodology uses augmentation of resonance Rayleigh scattering spectrum at 345 nm by the add dapoxetine. The current approaches exhibit linearity between response and dapoxetine concentration over 0.2 – 2.5 µg/mL and 0.3 – 3.0 µg/mL for spectrofluorimetric and RRS methods, respectively. All variables affecting methods and complex formation were studied and precisely optimized. The criteria of validation were performed by the directives provided by International Conference on Harmonisation’s Guidelines (ICH) and limits of detection (LOD) were 0.06 and 0.05 µg/mL for spectrofluorimetric and RRS techniques, respectively. Finally, the approaches were applied with acceptable results for pharmaceutical formulation analysis.
Chapter 8: Facile application of fourier transform infrared spectroscopy for solid state analysis of milnacipran. Application to content uniformity
In this chapter; a facile, non-destructive, and economic IR spectroscopic method was validated for direct analysis of MLC. The suggested method depends on measuring the absorbance intensity of the carbonyl group of the cited drug at wavelength 1631 cm-1. Validation of the proposed method was carried out by following the ICH rules. The method provides a linear range between MLC concentration and absorbance at 1 – 15 mg/g. The values of the estimated quantitation and detection limits were 0.96 and 0.32 respectively. The method was applied to MLC analysis of the dosage form successively and the percentage of recovery was 98.08 ± 1.76.