Biosynthesis and stereoselective analysis of (−)- and (+)-zaltoprofen glucuronide in rat hepatic microsomes and its application to the kinetic analysis

Wang, Haina; Ji, Jianbo; Zeng, Su

doi:10.1016/j.jchromb.2011.06.043

Cited by 6 publications

(1 citation statement)

References 35 publications

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“…The characterization of the enantiomeric enrichment requires a large number of constants and therefore complicates comparative analysis. (Ш) The third approach operates with enzyme kinetic analysis which provides the K m and V max Michaelis Menten kinetic constants for the individual enantiomers 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 . This approach forces the use of pure enantiomer standard solutions in order to examine the influencing and interfering effects arising from the chiral recognition of the enzymes binding site.…”

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confidence: 99%

Applicability of the Rayleigh equation for enantioselective metabolism of chiral xenobiotics by microsomes, hepatocytes and in-vivo retention in rabbit tissues

Jammer

Gelman

Lev

2016

Sci Rep

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In this study we propose a new approach for analyzing the enantioselective biodegradation of some antidepressant drugs mediated by human and rat liver microsomes by using the Rayleigh equation to describe the enantiomeric enrichment−conversion dependencies. Analysis of reported degradation data of additional six pesticides, an alpha blocker and a flame retardant by microsomes or hepatocytes in vitro reaffirmed the universality of the approach. In all the in vitro studied cases that involved enantioselective degradation, a Rayleigh dependence of the enantiomeric enrichment was observed. Published data regarding in vivo retention of myclobutanil in liver, kidney, muscle and brain tissues of rabbits following injection of the racemate were remodeled showing prevalence of the Rayleigh law for the chiral enrichment of the fungicide in the various tissues. This approach will revolutionize data organization in metabolic pathway research of target xenobiotics by either liver microsomes, hepatocytes or their organ-specific in vivo retention. The fact that the enantiomeric enrichment as a function of the conversion can be described by a single quantifier, will pave the road for the use of structure activity predictors of the enantiomeric enrichment and for mechanistic discrimination based on parametric dependence of the quantifier.

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