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- W2766979851 abstract "An efficient screening assay was developed and validated for simultaneous assessment of compound-mediated inhibition of six major human cytochrome P450 (CYP) enzymes. This method employed a cocktail of six probe substrates (i.e., phenacetin, amodiaquine, diclofenac, S-mephenytoin, dextromethorphan and midazolam for CYP1A2, 2C8, 2C9, 2C19, 2D6 and 3A4, respectively) as well as individual prototypical inhibitors of the six CYP enzymes in human liver microsomes under optimized incubation conditions. The corresponding marker metabolites (i.e., acetaminophen, N-desethylamodiaquine, 4-OH-diclofenac, 4-OH-S-mephenytoin, dextrorphan and 1-OH-midazolam) in the incubates were quantified using LC–MS/MS methods either by an internal standard (IS) calibration curve or a simplified analyte-to-IS peak area ratio approach. The results showed that the IC50 values determined by the cocktail approach were in good agreement with those obtained by the individual substrate approach as well as those reported in the literature. Besides, no remarkable difference was observed between the two quantification approaches. In conclusion, this new cocktail assay can be used for reliable screening of compound-mediated CYP inhibition." @default.
- W2766979851 created "2017-11-10" @default.
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- W2766979851 date "2017-10-01" @default.
- W2766979851 modified "2023-09-25" @default.
- W2766979851 title "Novel approach for evaluating pharmaceuticals toxicity using daphnia model: Analysis of the mode of cytochrome P450-generated metabolite action after acetaminophen exposure" @default.
- W2766979851 doi "https://doi.org/10.1016/j.toxlet.2017.07.568" @default.
- W2766979851 hasPublicationYear "2017" @default.
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