Dokument: Development and validation of a low-volume LC-HRMS assay for the analysis of aldosterone, its precursor and main metabolite tailored for paediatric research in a GCLP-compliant environment
| Titel: | Development and validation of a low-volume LC-HRMS assay for the analysis of aldosterone, its precursor and main metabolite tailored for paediatric research in a GCLP-compliant environment | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=50242 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20190717-091722-3 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Makowski, Nina [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Läer, Stephanie [Gutachter] Prof. Dr. Breitkreutz, Jörg [Gutachter] | |||||||
| Stichwörter: | Aldosterone, 18-Hydroxycorticosterone, Tetrahydroaldosterone, Validation, Paediatric, LC-HRMS | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | The Renin–Angiotensin–Aldosterone System (RAAS) is a humoral circuit decisive for cardiovascular health. Dysregulation of this sensitive system has severe consequences and can, for example, lead to hypertension, heart failure and subsequently to higher mortality. Aldosterone is an important effector of this system, and the positive effect of RAAS-regulating pharmacotherapy on morbidity and mortality has been proven in adults. The impact of aldosterone on the paediatric organism is not yet sufficiently investigated, thus, a reliable statement on it cannot be made.
In the first part of this thesis, the results of a literature review on the currently published aldosterone concentrations in healthy children and children with heart failure are presented. An age dependency of aldosterone levels and low data density in children under the age of one year became apparent in healthy as well as diseased children. The heterogeneity of the data showed the urgent need for high-quality research to enable unambiguous conclusions. Further, a customised quality assurance system, tailored for the need of bioanalytics in paediatric pivotal studies, was developed to enable such high-quality research. The successful implementation of this quality system was demonstrated using as an example its application to aldosterone measurements in such a clinical investigation. The developed system was able to support the acquisition of high-quality, guideline-conforming pharmacodynamic data. At the same time, monitoring of the data acquisition is possible, which enables detection of possible quality fluctuations and to take countermeasures to ensure reliable data. Moreover, a bioanalytical method for the reliable determination of serum concentrations of aldosterone, its precursor 18-hydroxycorticosterone, and its main metabolite tetrahydroaldosterone via high performance liquid chromatography coupled to high resolution mass spectrometry was developed and validated according to current, international guidelines to enable the collection of needed high-quality paediatric data. The application, even in severely diseased children, has been enabled by the minimal sample volume utilised. The simultaneous determination of aldosterone, its precursor and its main metabolite can provide new insights into the maturing paediatric organism. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Klinische Pharmazie und Pharmakotherapie | |||||||
| Dokument erstellt am: | 17.07.2019 | |||||||
| Dateien geändert am: | 17.07.2019 | |||||||
| Promotionsantrag am: | 20.05.2019 | |||||||
| Datum der Promotion: | 02.07.2019 |
