Thesis
Of impurities, drugs and metabolites - ToF-SIMS application studies for use in the pharmaceutical sciences
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2020
- Thesis identifier
- T15899
- Person Identifier (Local)
- 201561217
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- This thesis aims to explore the use of Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for applications in the pharmaceutical sciences through three separate studies with different pharmaceutical applications. The first study investigated the use of ToF-SIMS for the surface characterisation of pharmaceutical crystals using 4-nitrophenol and 4-acetamidobenzoic acid impurity incorporations in acetaminophen (paracetamol) crystals. A range of impurity deposition scenarios were examined to study the impurity intensity and distribution patterns as well as impurity-induced changes to the crystal surfaces. In the second study, the characteristics of human coronary artery endothelial cells (HCAECs) before and after application of an anti-thrombotic drug were analysed using ToF-SIMS. A sample preparation method was developed to analyse the cells as well as identify and image the drug on the cell surface. Subsequently, untreated and treated cells were prepared using the trialled procedure to investigate the effects of the drug on the cells. The final study explored the use of ToF-SIMS for bacterial analysis, in particular agar-based bacteria and the tracking of bacterial metabolites. In this scenario, various sample preparation and drying methods were trialled and the most successful method applied to attempt the identification and tracking of tetracycline, a known streptomyces metabolite and antibiotic, in the bacterial growth medium. In addition to the ToF-SIMS experimental studies, a software tool for the selection of spectral pre-processing methods for NIR and other spectral applications was developed and assessed. The software toolbox enables a design-of-experiment-centred approach to selecting viable pre-processing methods to correct spectral data prior to further usage in applications such as regression modelling. Two data use-cases are presented that stem from the chemical and pharmaceutical sciences and demonstrate the applicability of the tool.
- Advisor / supervisor
- Gilmore, Ian
- Nordon, Alison
- Johnston, Blair
- Resource Type
- DOI
- Funder
- Managing organisation
- EPSRC Future Manufacturing Hub for Continuous Manufacturing and Crystallisation
- National Physical Laboratory
Relazioni
Articoli
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PDF of thesis T15899 | 2021-07-28 | Pubblico | Scaricare |