Evaluation of the effect of Bovis Calculus Artifactus on eight rat liver cytochrome P450 isozymes using LC-MS/MS and cocktail approach

Bovis Calculus Artifactus (BCA) is the main substitute for natural bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities unknown. This study was investigate eight rat hepatic microsomal CYPisozymes evaluate potential interactions using cocktail approach.Metabolites isoform probe substrates CYP isozymes were quantified by LC-MS/MS. method validated incubating known inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual substrate liver microsomes. formation rates corresponding metabolites determined activity each isozyme.The results showed that has different degrees inhibitory four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p   0.05). Attention should be paid BCA-drug careful monitoring appropriate dosage adjustments concurrent use drugs which are metabolized CYP1A2, CYP2C19, CYP3A4. Abbreviations: BCA, bovis calculus artifactus; CYP, P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Calculus; QC, quality control; T CM, Chinese medicine.