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  • Title: Liquid chromatographic-electrospray mass spectrometric determination (LC-ESI-MS) of phase II metabolites of flobufen in rat liver microsomes-Chiral discrimination.
    Author: Babú YN, Nemec M, Solich P, Wsól V.
    Journal: Talanta; 2008 Apr 15; 75(2):494-502. PubMed ID: 18371912.
    Abstract:
    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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