dc.contributor.author
Harps, Lukas Corbinian
dc.contributor.author
Jendretzki, Annika Lisa
dc.contributor.author
Wolf, Clemens Alexander
dc.contributor.author
Girreser, Ulrich
dc.contributor.author
Wolber, Gerhard
dc.contributor.author
Parr, Maria Kristina
dc.date.accessioned
2023-11-28T13:56:24Z
dc.date.available
2023-11-28T13:56:24Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/41637
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-41357
dc.description.abstract
The aim of this study was to develop and optimize a chiral HPLC-MS/MS method for quantitative analysis of (R)-/(S)-salbutamol and (R)-/(S)-salbutamol-4′-O-sulfate in human urine to allow for bioanalytical quantitation of the targeted analytes and investigations of stereoselectivity in the sulfonation pathway of human phase Ⅱ metabolism. For analytical method development, a systematic screening of columns and mobile phases to develop a separation via enantiomerically selective high performance liquid chromatography was performed. Electrospray ionization settings were optimized via multiple-step screening and a full factorial design-of-experiment. Both approaches were performed matrix-assisted and the predicted values were compared. The full factorial design was superior in terms of prediction power and knowledge generation. Performing a longitudinal excretion study in one healthy volunteer allowed for the calculation of excretion rates for all four targeted analytes. For this proof-of-concept, either racemic salbutamol or enantiopure levosalbutamol was administered perorally or via inhalation, respectively. A strong preference for sulfonation of (R)-salbutamol for inhalation and peroral application was found in in vivo experiments. In previous studies phenol sulfotransferase 1A3 was described to be mainly responsible for salbutamol sulfonation in humans. Thus, in vitro and in silico investigations of the stereoselectivity of sulfotransferase 1A3 complemented the study and confirmed these findings.
en
dc.format.extent
24 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
enzymatic stereoselectivity
en
dc.subject
molecular docking
en
dc.subject
quality-by-design
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Development of an HPLC-MS/MS Method for Chiral Separation and Quantitation of (R)- and (S)-Salbutamol and Their Sulfoconjugated Metabolites in Urine to Investigate Stereoselective Sulfonation
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
7206
dcterms.bibliographicCitation.doi
10.3390/molecules28207206
dcterms.bibliographicCitation.journaltitle
Molecules
dcterms.bibliographicCitation.number
20
dcterms.bibliographicCitation.originalpublishername
MDPI
dcterms.bibliographicCitation.volume
28
dcterms.bibliographicCitation.url
https://doi.org/10.3390/molecules28207206
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Pharmazie
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refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
de
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1420-3049