Liquid chromatographic-electrospray mass spectrometric determination (LC-ESI-MS) of phase II metabolites of flobufen in rat liver microsomes-Chiral discrimination
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
18371912
DOI
10.1016/j.talanta.2007.11.039
PII: S0039-9140(07)00807-7
Knihovny.cz E-zdroje
- MeSH
- butyráty analýza MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu Rattus MeSH
- potkani Wistar MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- butyráty MeSH
- flobufen MeSH Prohlížeč
Glucuronidation of the non-steroidal anti-inflammatory chiral drug flobufen and its major metabolite M17203 has been implicated as an important mechanism of flobufen elimination. To characterize flobufen metabolism by O-glucuronidation, new liquid chromatographic method (LC) coupled with ESI-MS was developed to detect the conjugates of flobufen and its metabolites formed in vitro in rat liver microsomes. Discovery DSC-18 LT cartridge columns were utilized for solid phase extraction (SPE) and Discovery C18 column (150 mm x 2.1 mm, 5 microm particle size) was used for LC separation. Chiral inversion of flobufen and its metabolites enantiomers was checked by special 1-allyl-(5R,8S,10R)-terguride column (150 mm x 4.6 mm). O-Glucuronidation of the S-enantiomer displayed a typical Michaelis-Menten kinetics, whereas the R-enantiomer exhibited a substrate inhibition type of kinetics. The study of glucuronidation of M17203 led to kinetics with sigmoidal characteristics.
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