الفهرس 
Part I: IntroductionOnly 14 pages are availabe for public view
 |  | from | 214 |  |  |
| | | from | 214 | | |
Abstract
The present thesis is concerned with the development of new spectrofluorimetric and voltammetric methods for the determination of two DPP-4 inhibitors, antidiabetic drugs, LNG, and ALO in their pure, tablet forms and biological fluids. The study involves three parts:
Part I: Introduction
This part provides a brief overview of diabetes, type 2 diabetes, DPP-4 inhibitors, the physical and pharmacological properties of LNG and ALO. This part also includes a summary of the literature review concerning the reported analytical methods for determining the cited drugs.
At the end of the introduction, the aim of the thesis is illustrated, and the scope of the investigation is outlined.
Part II Spectrofluorometric Methods:
This part is comprised of two chapters:
Chapter I: Diarylpyrrolone Based Fluorophore for The selective Spectrofluorometric Method for Determination of Linagliptin Antidiabetic Drug in Pharmaceutical Tablets
In this chapter, a simple and sensitive spectrofluorometric method was developed and validated to determine LNG. The method employed the interaction of the primary amino group of the cited drug with fluorescamine reagent in aqueous borate buffer (pH 8.5) to produce a highly fluorescent product. The emission of the formed product was measured at 479 nm after excitation at 390 nm.
Different experimental parameters that may affect the product formation or its fluorescence intensity were investigated and adjusted. The method has good linearity in the concentration range of 0.2 – 2.0 μg mL-1 of LNG with a detection limit of 0.079 μg mL-1. The performance of the developed method was evaluated according to the International Council for Harmonization (ICH). The method was successfully applied for the analysis of tablets dosage form that contained the cited drug. The results of the study were compared with the reported method and indicated good accuracy and precision of the proposed procedure.
Chapter II: Spectrofluorometric Determination of Alogliptin an Anti-diabetic Drug in Pure and Tablet Form by Using Fluorescamine, a Fluorogenic Agent: Application to Content Uniformity Test
In this chapter, ALO was reacted with fluorescamine in a slightly alkaline medium (borate buffer, pH 8.8) to form a highly fluorescent product. The emission of this product was measured at 477 nm (λex = 387 nm). Based on this reaction, a simple spectrofluorimetric method was developed.
The linear range between the fluorescence intensity and the drug concentration was 0.1 – 0.5 μg mL−1 with a good correlation coefficient (0.9986). Limits of detection and quantitation were 22 and 72 ng mL−1, respectively. Guidelines of the International Council for Harmonization were followed to validate the developed method with acceptable results. ALO content was determined successfully in its commercial dosage form using the fluorescamine method with good recovery (98.60 – 101.26 %). The method has excellent accuracy and precision compared with the reported method as assessed using Student’s t-test and Fisher’s variance test. The method was applied successfully for the content uniformity test with high recovery and low relative standard deviation.
Part III Voltammetric Methods
This part contains four chapters. Each chapter describes the electrochemical method(s) to determine LNG in pure, tablets, and biological fluids.
Chapter 1: Square Wave Adsorptive Anodic Stripping Voltammetric Determination of Antidiabetic Drug Linagliptin in Pharmaceutical Formulations and Biological Fluids Using Pencil Graphite Electrode
The chapter describes the development of a square wave anodic stripping voltammetric method to determine LNG using the pencil graphite electrode (PGE).
Cyclic voltammetry (CV) was applied to study the electrochemical behavior of LNG in Teorell-Stenhagen buffer (pH = 5.5) containing 0.1 M NaClO4 as a supporting electrolyte, LNG yields an irreversible well–defined oxidation peak at about 1.2 V vs. Ag/AgCl electrode.
Different parameters such as pH, buffer type, supporting electrolyte, accumulation potential, scan rate, and accumulation time were tested and optimized. By using square wave adsorptive anodic stripping voltammetry, it was found that the peak current was varied linearly over the LNG concentration range of 0.24 – 5.20 µg mL–1 (R = 0.9994). The limits of detection and quantification were 0.10 and 0.33 µg mL–1, respectively. The proposed procedure exhibits good precision, selectivity, simplicity, sensitivity, low cost, and stability. The method was applied successfully to determine LNG in pharmaceutical formulations (tablets) and biological fluids (spiked human urine and plasma samples).
Chapter 2: Square Wave Anodic Voltammetric Determination of Antidiabetic Drug Linagliptin Using Copper Microparticles Modified Pencil Graphite Electrode in The Dosage Form and Biological Fluids
In this chapter, a new simple, cheap, and rapid method with improved sensitivity for LNG quantification was carried out on a pencil graphite electrode modified with copper microparticles (Cu-PGE).
The preparation of the disposable modified electrode was performed by the electrodeposition of Cu-microparticles onto the pencil graphite electrode. The modified electrode is cheap, and the modification process is very simple.
The developed SWV method has a linear response range from 47 - 284 ng mL-1 of LNG with a correlation coefficient of 0.9995. The detection and quantitative limits were 6.0 and 20.0 ng mL-1, respectively. The optimum working conditions for the determination of the drug were established. The proposed method was applied to determine LNG in the dosage form, spiked urine, and spiked plasma samples, and the obtained results were compared with the reported method.
Chapter 3: A Glassy Carbon Electrode for Determination of Linagliptin Antidiabetic Drug in Pure, Tablets and Some Biological Fluids by Adsorptive Stripping Voltammetry
The chapter provides a fast, simple, and inexpensive analytical method for the determination of LNG using a square wave adsorptive anodic stripping voltammetric technique (SWAAdsSV) with glassy carbon electrode (GCE) as a working electrode.
The experimental and instrumental parameters were studied and adjusted to ensure the validity of the method. The method has very good linearity (r = 0.9987), wide concentration range (0.047 - 2.65 µg mL-1), low detection limit (83.0 ng mL-1), and low quantitation limit (277.0 ng mL-1). LNG was determined successfully in pharmaceutical tablets, spiked human urine, and plasma with % recoveries of 99.67, 91.96, and 92.78 %, respectively. The accuracy and precision of the method were compared with the reported method. The method is more sensitive than most of the other reported electrochemical methods.
Chapter 4: The Utility of Adsorptive Square-Wave Stripping Voltammetry to Determine Linagliptin Antidiabetic Drug Using Graphene Oxide Modified Glassy Carbon Electrode: Application on Dosage Form and Biological Fluids
This chapter is devoted to constructing a simple and highly sensitive adsorptive square-wave stripping voltammetric (ASWSV) technique for the determination of LNG.
The glassy carbon electrode was modified with graphene oxide to increase the sensitivity of the electrode (GO-GCE).
The method was used successfully to determine the drug in pure form, tablets, spiked urine, and plasma with an efficient recovery 99.80, 93.40, and 89.67, respectively. Various experimental and instrumental parameters were investigated and adjusted to ensure the validity of the method. The proposed method has a range of 9.45 – 103.96 ng mL-1, with a good correlation coefficient of 0.9980. The limits of detection and quantitation were 4.0 and 14.0 ng mL-1, respectively. This method can be applied easily to determine Linagliptin in different research centers.
In addition, the thesis consists of 214 pages, includes; (44) tables, (52) figures, and (210) references, and ends with an English and Arabic Summaries.