الفهرس 
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Abstract
This thesis presents new analytical methods for determination monosodium glutamate in foods, pharmaceutical dosage form and human plasma. It consists of three parts: Part I This part describes a general introduction about glutamic acid (Monosodium glutamate) and different methods that have been reported for determination of glutamic acid. Part II This part deals with the development of two spectrophotometric methods for determination of monosodium glutamate in different food matrices and pediatric syrup dosage form. The first method is based on the reaction between monosodium glutamate and 1, 2-naphthoquinoe-4-sulfonate and in alkaline medium through aromatic substitution reaction mechanism to give colored derivative which can be measured at max 475nm. Different parameters affecting the reaction were optimized using OFAT approach. The method was validated according to ICH guidelines. The developed spectrophotometric method was linear over the concentration range of 5–35 μg/mL with limit of quantitation and limit of detection of 2.719 μg/mL and 0.897 μg/mL respectively. The second method is based on the reaction between monosodium glutamate and ascorbic acid by coupling reaction to give colored condensation product which can be measured at max 387nm. The reaction was optimized using 23 full factorial design. The method was validated regarding ICH guidelines. The developed spectrophotometric method was linear over the concentration range of 1–14 μg/mL with limit of quantitation and limit of detection of 1.325 μg/mL and 0.437 μg/mL respectively. Both methods were successfully applied for determination of monosodium glutamate in pediatric syrup dosage form, instant noodles and stock cubes. To avoid interference from the matrix and because of the unknown concentration of monosodium glutamate, standard addition method was applied. Analytical Eco-scale is used to assess the greenness of the developed methods. Different analytical procedure parameters (amounts of reagents, hazards, energy, and waste) were evaluated. Penalty points were assigned for each parameter. Both methods were assumed to be excellent green methods.The developed spectrophotometric methods were compared to reported high performance liquid chromatography method using the student’s t-test and F-test. The experimental t- and F- values did not exceed the theoretical values at 95% confidence level, indicating the absence of any significant difference between the developed and comparison methods. Part III This part deals with the development of liquid chromatography-mass spectroscopy method for determination of twenty L-amino acids in human plasma. The method is based on using 5-sulfosalicylic acid as protein precipitating agent. Three cephalosporin (cefalexin, cefadroxil and cefaclor) were used as internal standards to cover the wide linearity range of all amino acids. Mass detection parameters were optimized. Under the positive ESI mode, all the amphoteric amino acids demonstrated high MS responses. chromatographic analysis was achieved on the Luna PFP column (2.0 × 50 mm, 5-μm; Phenomenex, Torrance, USA) with security guard cartridges (PFP 4.0 × 2.0mm). The flow rate was 0.2 mL/min, with the column temperature being kept at 40 ° C. The mobile phase consists of (A) water containing (0.1%, v/v) formic acid and (B) methanol containing (0.1%, v/v) formic acid. Separation was achieved using a time programmed gradient elution.The injection volume was 10-μL. The linearity range of the developed method was from 2.5 nM to 1500 nM for all amino acids with a correlation coefficient (r) ≥0.9971. The developed LC-MS/MS method was used to monitor amino acids concentrations in plasma of schizophrenic patients in initially diagnosed patients compared to healthy individuals. The results reveal that some amino acids concentrations such as glutamic, proline, tyrosin, valine, lysine, threonine, asparagine and glutamine changed in initially diagnosed patients compared to controls. The thesis contains 17 tables, 27 figures, 2 schemes and 99 references in addition to Arabic summary.