الفهرس 
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Abstract
This thesis is concerned with enhancing the sensitivity of selected analytical methods for determination of some antidiabetic drugs, via usage of derivatization reaction, dispersive liq-liq microextraction extraction technique, sensitive detectors and different protein precipitating agent prior to analysis. This thesis consists of four parts: Chapter I: General introduction This section discusses how sensitivity of an analytical method could be improved by different ways such as detector selection, pre-concentration by extraction, or derivatization. Chapter II : Ultrasound-assisted dispersive liquid–liquid microextraction for determination of three gliflozins in human plasma by HPLC/DAD A new method applying dispersive liquid-liquid microextraction combined with HPLC/DAD has been described for the determination of empagliflozin, dapagliflozin and canagliflozin in human plasma in a single chromatographic run. The proposed method provides high enrichment factors within an analysis time of 5 min. This work presents the first report for extraction and determination of EMPA, DAPA and CANA by DLLME, which is a powerful tool for increasing the sensitivity of analysis with short assay time and low solvent consumption. The method is suitable for biomedical analysis, bioavailability and pharmacokinetic studies of these gliflozins. Application of this method for studying different drug-drug and drug-food interactions of this class of oral antidiabetics will be the focus of our future research.Chapter III: Tetrahydrofuran as a novel protein precipitating agent for preparation of plasma samples; a comparative study Tetrahydrofuran has been successfully used as a plasma protein precipitating agent for sample preparation before biomedical analysis. The high water miscibility of THF helps destroy the hydration layer around the proteins, and decrease the repulsive forces, which induces protein aggregation and precipitation. The efficiency of THF in protein precipitation was evaluated using two reported methods, and the results were compared with other common precipitants. The performance of THF was found comparable to the performance of acetonitrile/methanol and observably better than TFA. The %recoveries of seventeen different drugs, prepared using the four precipitating agents were calculated and compared. THF was found superior in six drugs including carboplatin, empagliflozin, prednisolone acetate, remdesivir, silver sulfadiazine, and triamcinolone acetonide. These results indicated that THF could be a promising plasma protein precipitating agent that could be used as a cheap alternative to acetonitrile or methanol. This work introduced THF to the realm of sample deproteinization and widen the scope of protein precipitation to include other applications that were not successfully performed using common precipitating agents. Chapter IV: A UPLC/DAD method for simultaneous determination of empagliflozin and three related substances in spiked human plasma A new, fast, sensitive, selective and fully validated UPLC/DAD method was developed for analysis of EMPA and its three related substances in spiked human plasma. Favorable advantages of the proposed UPLC method were found in significant reduction in elution time as well as.