Document Detail

Structural elucidation of N-oxidized clemastine metabolites by liquid chromatography/tandem mass spectrometry and the use of Cunninghamella elegans to facilitate drug metabolite identification.
MedLine Citation:
PMID:  20411584     Owner:  NLM     Status:  MEDLINE    
Cunninghamella elegans is a filamentous fungus that has been shown to biotransform drugs into the same metabolites as mammals. In this paper we describe the use of C. elegans to aid the identification of clemastine metabolites since high concentrations of the metabolites were produced and MS(n) experiments were facilitated. The combination of liquid chromatography and tandem mass spectrometry with two different ionization techniques and hydrogen/deuterium exchange were used for structural elucidation of the clemastine metabolites. Norclemastine, four isomers of hydroxylated clemastine, and two N-oxide metabolites were described for the first time in C. elegans incubations. The N-oxidations were confirmed by hydrogen/deuterium exchange and deoxygenation (-16 Da) upon atmospheric pressure chemical ionization mass spectrometry. By MS(n) fragmentation it was concluded that two of the hydroxylated metabolites were oxidized on the methylpyrridyl moiety, one on the aromatic ring with the chloro substituent, and one on the aromatic ring without the chlorine.
Annica Tevell Aberg; Helena Löfgren; Ulf Bondesson; Mikael Hedeland
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Rapid communications in mass spectrometry : RCM     Volume:  24     ISSN:  1097-0231     ISO Abbreviation:  Rapid Commun. Mass Spectrom.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-22     Completed Date:  2010-08-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8802365     Medline TA:  Rapid Commun Mass Spectrom     Country:  England    
Other Details:
Languages:  eng     Pagination:  1447-56     Citation Subset:  IM    
Copyright Information:
Copyright 2010 John Wiley & Sons, Ltd.
Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala, Sweden.
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MeSH Terms
Chromatography, High Pressure Liquid / methods*
Clemastine / analysis*,  metabolism,  urine
Cunninghamella / metabolism*
Deuterium Exchange Measurement
Drug Discovery / methods
Tandem Mass Spectrometry / methods*
Reg. No./Substance:

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