The primary purpose of this study was to investigate the combination of experimental and computational methods in the search for reproducible colloidal surface-enhanced Raman scattering of pharmaceutical compounds. In the search for optimal experimental conditions for colloidal surface-enhance Raman scattering, the amphipathic β-blocker propranolol was used as the target molecule. Fractional factorial designs of experiments were performed and a multiobjective evolutionary algorithm was used to find acceptable solutions, from the results, that were Pareto ranked. The multiobjective evolutionary algorithm suggested solutions outside of the fractional factorial design and the experiments were then performed in the laboratory. The results observed from the suggested solutions agreed with the solutions that were found on the Pareto front. One of the experimental conditions observed on the Pareto front was then used to determine the practical limit of detection of propranolol. The experimental conditions that were chosen for the limit of detection took into account reproducibility and enhancement, the two most important parameters for analytical detection using surface-enhanced Raman scattering. The principal conclusion to this study was that the combination of computational and experimental methods can reduce the need for experiments by > 96% and then selecting solutions from the Pareto front improved limit of detection by a factor of 24.5 when it was compared to the previously reported limit of detection for propranolol. Using the same experimental conditions that were used for the limit of detection, these experiments were extended to plasma spiked with propranolol in order to test detection of this pharmaceutical in biofluids. Concentrations of propranolol were prepared using plasma as the solvent and measured for detection using colloidal surface-enhanced Raman scattering. Detection was determined as
|Date of Award||31 Dec 2012|
- The University of Manchester
|Supervisor||Ewan Blanch (Supervisor) & Royston Goodacre (Supervisor)|
- MOEA, SERS, fitness function, FWHM, propranolol
- surface-enhanced Raman scattering; biofluids; plasma
- Raman spectroscopy; ROA; DFT calculations; acetylation and a- and ß-N-acetyl-L-Asp-L-Glu
- Raman spectroscopy; Raman Optical Activity; N-acetyl-L-Asp; N-acetyl-L-Glu; acetylation; deuteration.