New analytical LC-mass spectrometry methodologies for the quali-quantitative determination of natural substances and drugs in complex matrices

Spinozzi, Silvia (2015) New analytical LC-mass spectrometry methodologies for the quali-quantitative determination of natural substances and drugs in complex matrices , [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Chimica, 27 Ciclo. DOI 10.6092/unibo/amsdottorato/6997.
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This thesis reports an integrated analytical and physicochemical approach for the study of natural substances and new drugs based on mass spectrometry techniques combined with liquid chromatography. In particular, Chapter 1 concerns the study of Berberine a natural substance with pharmacological activity for the treatment of hepatobiliary and intestinal diseases. The first part focused on the relationships between physicochemical properties, pharmacokinetics and metabolism of Berberine and its metabolites. For this purpose a sensitive HPLC-ES-MS/MS method have been developed, validated and used to determine these compounds during their physicochemical properties studies and plasma levels of berberine and its metabolites including berberrubine(M1), demethylenberberine(M3), and jatrorrhizine(M4) in humans. Data show that M1, could have an efficient intestinal absorption by passive diffusion due to a keto-enol tautomerism confirmed by NMR studies and its higher plasma concentration. In the second part of Chapter 1, a comparison between M1 and BBR in vivo biodistribution in rat has been studied. In Chapter 2 a new HPLC-ES-MS/MS method for the simultaneous determination and quantification of glucosinolates, as glucoraphanin, glucoerucin and sinigrin, and isothiocyanates, as sulforaphane and erucin, has developed and validated. This method has been used for the analysis of functional foods enriched with vegetable extracts. Chapter 3 focused on a physicochemical study of the interaction between the bile acid sequestrants used in the treatment of hypercholesterolemia including colesevelam and cholestyramine with obeticolic acid (OCA), potent agonist of nuclear receptor farnesoid X (FXR). In particular, a new experimental model for the determination of equilibrium binding isotherm was developed. Chapter 4 focused on methodological aspects of new hard ionization coupled with liquid chromatography (Direct-EI-UHPLC-MS) not yet commercially available and potentially useful for qualitative analysis and for “transparent” molecules to soft ionization techniques. This method was applied to the analysis of several steroid derivatives.

Tipologia del documento
Tesi di dottorato
Spinozzi, Silvia
Dottorato di ricerca
Scuola di dottorato
Scienze chimiche
Settore disciplinare
Settore concorsuale
Parole chiave
berberine; berberrubine; metabolism; biodistribution; pharmacokinetics; HPLC-MS/MS; bile fistula rat; physicochemical properties;glucosinolates; nutraceuticals; functional food;OCA; coadministration; bile acid sequestrant; Langmuir isotherm;Direct-EI; steroids
Data di discussione
8 Aprile 2015

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