الفهرس 
Part I: General introductionOnly 14 pages are availabe for public view
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Abstract
In this thesis, two anticonvulsant drugs namely gabapentin and pregabalin had been studied. The present thesis falls in four parts:
Part I: General Introduction
This part provides a general introduction about the investigated drugs such as, pharmaceutical importance, chemical structure and a review for the analytical techniques that have been used for 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 presented.
Part II: A highly sensitive spectrofluorimetric method for determination of gabapentin and pregabalin in pure forms and pharmaceutical dosage forms.
This part is devoted to develop a new spectrofluorimetric method for determination of gabapentin and pregabalin in pure form and pharmaceutical dosage forms. The method is based on derivatization reaction between o-phthalaldehyde in presence of 2-mercaptoethanol and the primary amino group of gabapentin and pregabalin through forming a yellow fluorescent product measured at 431 nm (excitation at 335 nm). Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The linear range was 25.0 – 125.0 ng ml-1 for both studied drugs. The detection limits were 3.4 and 4.6 ng ml-1, and the quantitation limit were 11.2 and 15.5 ng ml-1, for gabapentin and pregabalin, respectively. The developed method was successfully applied for determination of gabapentin and pregabalin in their commercial capsules without interference from common excipients.
Part III: Development of spectrofluorimetric method for determination of certain antiepileptic drugs through condensation with ninhydrin and phenyl acetaldehyde
This part describes simple, new and sensitive spectrofluorimetric method for determination of gabapentin and pregabalin based on condensation reaction of the primary amino group of the studied drugs with ninhydrin and phenyl acetaldehyde in Teorell and Stenhagen buffer medium. The formed yellow fluorescent product exhibits excitation and emission maxima at 375 and 470 nm, respectively. The different experimental parameters affecting the formation and stability of the reaction product were carefully studied and optimized. The fluorescence intensity of the reaction product is directly proportional with the concentration of the cited drugs over the range 5.0 – 25.0 µg ml−1 for gabapentin and 2.0 -30.0 µg ml−1 for pregabalin with excellent correlation coefficients (0.9999 for both drugs). The lower quantitation limits were 1.49 and 0.63 µg ml−1 for gabapentin and pregabalin; respectively. The proposed method was successfully applied for determination of gabapentin and pregabalin in commercial capsules with good percentage recovery.
Part IV: The utility of acetylbutyrolactone for spectrofluorimetric determination of two gamma-aminobutyric Acid (GABA) analogues
This part is concerned with the development of simple, selective and economic method for determination of two gamma-aminobutyric acid (GABA) analogues containing primary aliphatic amino group (gabapentin and pregabalin). The proposed method simply depends on the condensation of the amino group of the drugs with 2-acetylbutyrolactone to form Schiff bases which have strong fluorescence activities at 440 nm after excitation at 380 nm. The different reaction parameters that affect the development and stability of the formed Schiff base have been deeply investigated and optimized. The fluorescence-concentration plots were rectilinear over the range of 20.0 - 100.0 µg ml-1 for gabapentin and 10.0 -100.0 µg ml-1 for pregabalin with high correlation coefficients (0.9998) for gabapentin and (0.9999) for pregabalin. The lower quantitation limits were 2.93 and 1.93 µg ml−1 for gabapentin and pregabalin, respectively. Determination of gabapentin and pregabalin in the commercial capsules were achieved using the proposed method with excellent recoveries (100.22% for Gaptin® capsules and 100.28% for Lyrolin® capsules) and high degree of accuracy.
All the developed methods were validated according to ICH guidelines, regarding linearity, range accuracy, precision, limit of detection, limit of quantitation and robustness. All the results were satisfactory.
The thesis includes a list of 188 references; in addition the thesis comprises 26 tables, 19 figures and 3 schemes, as well as summary in English and Arabic.