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Title: Development of quantification methods and evaluation of drugs photostability in the presence of cyclodextrin polymer and human serum albumin protein
Author: Benson, Georgina
ISNI:       0000 0004 7968 9444
Awarding Body: De Montfort University
Current Institution: De Montfort University
Date of Award: 2019
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This study aims to approach common issues encountered when detecting pharmaceuticals in surface waters and biofluids, using six compounds, Ethyl-3-aminobenzoate (3AB), Ethyl-2-aminobenzoate (2AB), Benzocaine (BZ), Mangiferin (MA), Tranilast (TR) and Axinitib (AXI). The work can be seen as involving two main parts: an analytical and a physicochemical part. In the analytical part two fluorimetric methods were developed to facilitate the detection of the compounds in different media. In the first section new quantification methods were developed to determine the drugs and molecules at the ppt level in both water and a real sample (canal water). This method utilised β-CDP to increase the fluorimetric signal of the six compounds, up to ≈70 times. A recently proposed fluorimetric model was then used to characterise the drug-β-CDP inclusion complexes and stoichiometries, overcoming the limitations of the unknown molecular weight of β-CDP. This model was able to indicate that each compound formed either partial or multiple complexes with β-CDP, allowing for non-integer values to be considered, which could not be obtained using previous inclusion complex models. To enable the compounds to be quantified in the presence of HSA, the decrease in the fluorimetric signal induced by an interaction between each of the six compounds and HSA was utilised. Through use of a novel application of Stern-Volmer equations, each compound was able to be successfully detected in the presence of HSA, providing a rapid, easy way to detect these compounds, without removal of the protein. The proposed analytical methods using cyclodextrin nanosponge and human serum protein were proven to be robust and reliable, and each method was able to detect concentrations of the compounds of ≈0.06ppb and ≈1ppb, respectively, representing a new way to improve detection and quantification of organic molecules, which could be extended to compounds other than those used in this study. The physicochemical part dealt with the characterisation of the selected drugs and molecules in the absence and presence of nanosponges and human serum protein. After studying the evolution of the photodegradation of the compounds in a set of specific conditions, the -order kinetics tool made it possible to prove that the quantum yield of the forward and reverse photoreaction of TR in ethanol was wavelength dependent, increasing from 245nm-350nm, and that TR could be employed as an actinometer for the determination of unknown reaction parameters. In addition the photostability of the studied molecules (TR and AXI) was significantly improved (more than 90% reduction of degradation) upon addition of increasing concentration of nanosponge or human serum albumin. This is particularly important for drug formulation and might explain the higher photostability of drugs in the blood stream. In conclusion, each developed method was able to assist with the detection of the compounds in the outlined media, providing advantages that may be beneficial for future research of pharmaceuticals in biofluids and surface waters.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available