Add time:07/19/2019         Source:sciencedirect.com

Glucuronidation of the non-steroidal anti-inflammatory chiral drug flobufen (cas 112344-52-2) 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 × 2.1 mm, 5 μm 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 × 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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