| Strategic identification of in vitro metabolites of 13-desmethyl spirolide C using liquid chromatography/high-resolution mass spectrometry. | |
| | |
MedLine Citation:
|
PMID: 22223322 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
A strategy to identify metabolites of a marine biotoxin, 13-desmethyl spirolide C, has been developed using liquid chromatography coupled to high-resolution mass spectrometry (LC/HRMS). Metabolites were generated in vitro through incubation with human liver microsomes. A list of metabolites was established by selecting precursor ions of a common fragment ion characteristic of the spirolide toxin which was known to contain a cyclic imine ring. Accurate mass measurements were subsequently used to confirm the molecular formula of each biotransformation product. Using this approach, a total of nine phase I metabolites was successfully identified with deviations of mass accuracy less than 2 ppm. The biotransformations observed included hydroxylation, dihydroxylation, oxidation of a quaternary methyl group to hydroxymethyl or carboxylic acid groups, dehydrogenation and hydroxylation, as well as demethylation and dihydroxylation reactions. In a second step, tandem mass spectrometry (MS/MS) was performed to elucidate structures of the metabolites. Using the unique fragment ions in the spectra, the structures of the three major metabolites, 13,19-didesmethyl-19-carboxy spirolide C, 13,19-didesmethyl-19-hydroxymethyl spirolide C and 13-desmethyl-17-hydroxy spirolide C, were assigned. Levels of 13-desmethyl spirolide C and its metabolites were monitored at selected time points over a 32-h incubation period with human liver microsomes. It was determined that 13,19-didesmethyl-19-carboxy spirolide C became the predominant metabolite after 2 h of incubation. The stability plot of 13-desmethyl spirolide C showed first-order kinetics for its metabolism and the intrinsic clearance was calculated to be 41 μL/min/mg, suggesting first-pass metabolism may contribute to limiting oral toxicity of 13-desmethyl spirolide C. Copyright © 2012 John Wiley & Sons, Ltd. |
| | |
Authors:
|
Joseph P M Hui; J Stuart Grossert; Murray J Cutler; Jeremy E Melanson |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Rapid communications in mass spectrometry : RCM Volume: 26 ISSN: 1097-0231 ISO Abbreviation: Rapid Commun. Mass Spectrom. Publication Date: 2012 Feb |
Date Detail:
|
Created Date: 2012-01-06 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8802365 Medline TA: Rapid Commun Mass Spectrom Country: England |
Other Details:
|
Languages: eng Pagination: 345-54 Citation Subset: IM |
Copyright Information:
|
Copyright © 2012 John Wiley & Sons, Ltd. |
Affiliation:
|
National Research Council of Canada, Institute for Marine Biosciences, 1411 Oxford St., Halifax, Nova Scotia, B3H 3Z1, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reduced fragmentation in liquid injection field desorption/ionization Fourier transform ion cyclotro...
Next Document: A fast and selective method for anthocyanin profiling of red wines by direct-infusion pneumatic spra...