الفهرس 
General IntroductionOnly 14 pages are availabe for public view
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Abstract
The thesis investigates the development and validation of analytical methods for overcoming the challenges of determining low detectability drugs, i.e., medications lacking a chromophore or fluorophore, as well as high potency drugs in dosage form and biological fluids. Fluorescent carbon quantum dots, chemical derivatization, electrochemical techniques, and micellar liquid chromatography were used in these studies. The thesis is formed of four parts. Part I: General introduction This part provides an overview of the definition and applications of fluorescent carbon quantum dots, chemical derivatization, electrochemical methods, and micellar liquid chromatography in determination of low detectability drugs. Part Ⅱ: Spectroscopy approach for determination of low detectability drugs. This part is formed of three chapters. Chapter 1: Carbon quantum dots as a sensitive fluorescent probe for quantitation of pregabalin; application to real samples and content uniformity test This chapter introduces a new nano-sensor for detecting pregabalin (PG) in pharmaceutical capsules (Lyrica®) and biological fluids. A highly simple, green hydrothermal and fluorescent Carbon quantum CQDts dots was synthesized using Ascorbic acid (AA) as the carbon source which capped with ethylene glycol to form yellow emitters with highly fluorescence emission at 524 nm after excitation at 356 nm. The CQDts are verified by spectroscopic characterization such as transmission electron microscopy (TEM) and FT-IR spectra. This method is based on quenching of CQDts fluorescence in the presence of PG. Different variables that may affect the quenching of CQDts in the procedure, such as pH, buffer volume, and incubation duration, were studied. This analytical method was validated in accordance with ICH guidelines, and the Content Uniformity Test was carried out. PG was tested in concentrations ranging from 4.0 to 100μg/ mL. The limit of detection and quantitation were 1.12 and 3.39 μg/ mL respectively. proposed method could be used for both quality control and pharmacokinetic research for PG. This method was published in Luminescence,2022 Jan;37(1):170-176, https://doi: 10.1002/bio.4158. Chapter 2: The use of complex formation approach for spectrofluorimetric analysis of memantine hydrochloride with Safranin; Application to its tablets and human plasma. This chapter presented a new spectrofluorimetric method for the detection of memantine hydrochloride that was quick, accurate, and selective. The proposed method is based on a highly fluorescent complex formed by reaction of Mem-HCL with safranin. The fluorescent complex was extracted using chloroform under optimal conditions. The excitation and emission fluorescence intensities were measured at 520 nm and 549 nm, respectively. Mem-HCL was determined over concentrations ranging from 3 to 50 μg/ mL. The detection and quantification limits were respectively 0.03 and 2.61 μg/ mL. The suggested analytical approach was validated in accordance with ICH requirements and used to both Ebixa® dosage form and spiked human plasma. As a result, the proposed method is thought to be convenient for quality control determination as well as clinical laboratories. Chapter 3: Turning on fluorescent probe for sensitive detection of streptomycin in pure, pharmaceutical formulations and human plasma This chapter illustrates a spectrofluorimetric technique that used to determine strep in both pure form and pharmaceutical vials. This method depended on fluorescamine fluorescence being turned on as a result of its interaction with a primary amino group of strep. After excitation at 390 nm, the emitted fluorescence was measured at 482 nm in the presence of an aqueous borate buffer pH 8. The reason of the extremely fluorescent product was formation of diaryl pyrrolone cation with a planar structure. The fluorescence intensity was proportional to the drug concentration in the range of 100-600 ng/ mL. The proposed method was validated in accordance with ICH-guidelines. Detection and quantitation limits were determined to be 8.3 and 25.2 ng/ mL, respectively. This approach has various advantages over other methods, including the fact that it is faster, involves only one step of reaction, requires only one reagent, and can be performed at room temperature without heating. In addition, the described technique was used to determine streptomycin levels in human plasma. Part Ⅲ: Electrochemical approach for determination of low detectability drugs This part is formed from 1 chapter. Chapter 1: An Eco-Friendly Electrochemical Sensor made of glassy carbon electrode modified with ZnO nanoparticles and decorated with graphene oxide for the determination of vildagliptin in pure form, pharmaceutical dosage form, and spiked plasma: Inspection of the greenness of the proposed method This chapter presents a rapid, accurate, and selective voltammetric approach for determining VLD that uses a modified glassy carbon electrode containing ZnO nanoparticles and graphene oxide (ZNO-NPts / GOs/ GCE). The morphological characterization of the electrode was examined by transmission electron microscopy and also the electrochemical behavior of VLD was studied. Under optimal conditions, the determination of VID utilizing (ZNO-NPts / GOs/ GCE) sensors showed a linear correlation throughout the range of (15-150 μg/ mL), with LOD and LOQ equal 4.88, 14.8μg/ mL, respectively. This electrode (ZNO-NPts/GOs/GCE) had a good reproducibility, repeatability, and stability. Furthermore, the proposed approach was employed successfully to determine VID in pharmaceutical dosage tablet and human plasma with satisfactory recovery. The greenness of this method was also assessed using the green analytical procedure index (GAPI). Part Ⅳ: chromatographic approach for determination of low detectability drugs This part is formed from 1 chapter. Chapter 1: An ecofriendly green micellar HPLC-UV method for simultaneous determination of clindamycin phosphate and adapalene in pharmaceutical gel for acne treatment This chapter describes the development and validation of a quick, accurate, and highly sensitive environmentally friendly micellar liquid chromatography approach for the simultaneous detection of CID and ADA in bulk and mixed dosage gel form. The study was carried out using BDS HYPERSIL C18 (150 4.6 mm, 5m particle size) with a micellar mobile phase comprised of 0.07M SDS, 0.3% TEA, 0.02M orthophosphoric acid at pH 3.0, and 14% v/v isopropanol. The effluents have been monitored with UV detection at 210nm. The linearity ranges for CID and ADA were 100-500 and 10-50 μg/mL, respectively, with detection limits of 13.4 and 1.4 μg/mL. With high recoveries, the proposed method was employed to determine the two drugs in their laboratory manufactured co-formulated gel form. Furthermore, the ”green analytical procedure index (GAPI)” was used to assess the method greenness. This method has been proven to be extremely ecologically friendly. Also, this method was effectively used as a stability indicating method for estimating CID and ADA under various stressful conditions.