الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
This thesis is concerned with the development and validation of new different analytical methods for determination of some of selected antidiabetic drugs in pharmaceutical dosage forms and in biological fluids. Such methods can be categorized as follow :
• Spectrophotometric methods
• Spectrofluorimetric methods
• Liquid chromatography tandem mass spectrometry
According to the nature of drug and the purpose for analysis, the suitable method is chosen for its determination , developed, optimized and validated. For drugs lacking or having weak fluorophore , chemical derivatization was necessary.
The thesis consists of three parts :
Part I : General introduction and review of literature.
This part presents the aim of this study and general introduction about the drugs investigated throughout the whole thesis covering the structures ,chemical names ,molecular weight ,physical properties ,pharmacological actions and pharmacokinetics properties. Finally , a literature review describes the reported methods for analysis of the selected drugs either in a bulk form or in their pharmaceutical dosage forms or in biological fluids.
Part II : Development and validation of spectrofluorimetric methods for determination of Alogliptin benzoate and Linagliptin in bulk, dosage forms and biological fluids.
This part consists of two chapters :
Chapter 1 : Novel spectrofluorimetric quantification of Alogliptin benzoate in biofluids exploiting its interaction with 4-chloro-7-nitrobenzofurazan.
This chapter presents a validated spectrofluorimetric determination of Alogliptin benzoate through derivatization with 4-chloro-7-nitrobenzofurazan in borate buffer at pH 8.5 to produce a strong fluorescent derivative .
The developed method was successfully applied for determination of Alogliptin in Inhiglip® 12.5 mg tablet dosage form.
The developed method was also applied for determination of Alogliptin in spiked human plasma without interference from plasma protein using salting out assisted liquid liquid extraction for sample preparation and it has been applied in preliminary pharmacokinetics study in rats .
Chapter 2 : Novel spectrofluorimetric quantification of Linagliptin in biological fluids after derivatization with 4-chloro-7-nitrobenzofurazan.
In this chapter, a new spectrofluorimetric method for determination of Linagliptin was developed, optimized and validated .
The suggested method was based on reaction between the primary amino group of Linagliptin and 4-chloro-7-nitrobenzofurazan in borate buffer at pH 8.5 to produce a strong fluorescent derivative .
The developed method was successfully applied for determination of alogliptin in Trajenta® 5 mg tablet dosage form.
The method was also applied for determination of Linagliptin in spiked human plasma without interference from plasma protein using simple liquid liquid extraction for specimen preparation .
Part III : Development and validation of spectrophotometric methods and Liquid chromatography tandem mass spectrometry (LC-MS/MS) for simultaneous determination of Linagliptin and Pioglitazone HCl in laboratory synthetic mixtures and in biological fluids with pharmacokinetic and drug drug interaction studies .
This part consists of two chapters :
Chapter 1: Determination of Novel Promising Combination of Linagliptin and Pioglitazone HCl in Bulk and Laboratory Synthetic Mixture by Earth-Friendly Three Spectrophotometric Methods.
This chapter presents the development and validation of three spectrophotometric methods : First derivative spectrophotometry , Area under curve and Isosbestic point spectrophotometry for simultaneous determination of Linagliptin and Pioglitazone HCl in laboratory synthetic mixtures.
Chapter 2 : Liquid chromatography tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of linagliptin and pioglitazone HCl in rat plasma: Application to pharmacokinetic and drug-drug interaction studies.
This chapter presents a simple, robust, and sensitive reverse phase high performance liquid chromatography–electrospray ionization-tandem mass spectrometry (ESI-MS/MS) method for simultaneous determination of LIN and PIO in rat plasma using Alogliptin as internal standards (IS) . Prior chromatographic separation on an Agilent Eclipse Plus C18 (4.6×100 mm, 3.5 μm) using isocratic mobile phase system consisting of ammonium formate (pH 4.5) and Methanol at a flow rate of 0.7 mL min-1, within a run time of 5 min. The antidiabetic drugs were extracted from rat plasma using acetonitrile-induced protein precipitation technique. Multiple reaction monitoring in positive ion mode was used for quantitation of precursor to production at m/z 473.2→419.9 for LIN ,357.1→134.2 for PIO, and 340.3→116.1 for ALO. Method linearity was obeyed in the range of 1 to 100 and 1 to 1000 ng mL-1 for LIN and PIO, respectively. The developed method was validated in terms of accuracy, precision, selectivity, recovery, matrix effects, and stability as per US-FDA bioanalytical guidelines and successfully applied to clinical pharmacokinetic and drug-drug interaction (DDI) studies with a single oral administration of LIN and PI