Validated liquid chromatography–tandem mass spectrometry method for determination of totally nine probe metabolites of cytochrome P450 enzymes and UDP-glucuronosyltransferases

Lee, Jr Ting; Pao, Li-Heng; Hsiong, Cheng Huei; Huang, Pei Wei; Shih, Tiffany Ting-Fang; Hu, Oliver Yoa Pu

doi:10.1016/j.talanta.2012.12.023

Cited by 14 publications

(12 citation statements)

References 28 publications

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“…While the similarly indirect Nash method (Nash, 1953) does provide information regarding specific CYP isoenzymes, it is insufficiently sensitive to register most xenobiotic-induced changes. Indirect but isoenzyme-specific measurement is possible with high-performance liquid chromatography (Lahoz et al, 2008;Lee et al, 2013) and Western blot (LeCluyse, 2001), but these methods are complex and problematic because the amount of CYP protein is not directly proportional to CYP activity. Analytical methods based on 3 H-or 14 C-labeled drug substrates are accurate but require protective equipment, subsequent decontamination and specialised waste disposal (Zlokarnik et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

et al. 2017

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As considerable inter-species differences exist in xenobiotic metabolism, developing new pharmaceutical therapies for use in different species is fraught with difficulties. For this reason, very few medicines have been registered for use in rabbits, despite their importance in inter alia meat and fur production. We have developed a rapid and sensitive screening system for drug safety in rabbits based on cytochrome P450 enzyme assays, specifically CYP1A1, CYP1A2 and CYP3A6, employing an adaptation of the luciferin-based clinical assay currently used in human drug screening. Short-term (4-h) cultured rabbit primary hepatocytes were treated with a cytochrome inducer (phenobarbital) and 2 inhibitors (alphanaphthoflavone and ketoconazole). In parallel, and to provide verification, New Zealand white rabbits were dosed with 80 mg/kg phenobarbital or 40 mg/kg ketoconazole for 3 d. Ketoconazole significantly increased CYP3A6 gene expression and decreased CYP3A6 activity both in vitro and in vivo. CYP1A1 activity was decreased by ketoconazole in vitro and increased in vivo. This is the first report of the inducer effect of ketoconazole on rabbit cytochrome isoenzymes in vivo. Our data support the use of a luciferin-based assay in short-term primary hepatocytes as an appropriate tool for xenobiotic metabolism assays and short-term toxicity testing in rabbits.

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Section: Discussionmentioning

confidence: 99%

Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

et al. 2017

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“…The developed UPLC-MS/MS, which was used for the subsequent quantitation of the six probe drugs, showed a faster analysis time than conventional HPLC (Jerdi et al, 2004;Yao et al, 2007;Johansson et al, 2012) or LC-MS (Scott et al, 1999;Zhang et al, 2002;Yin et al, 2004;He et al, 2007;Lad, 2010;Hu et al, 2012;Oh et al, 2012;Lee et al, 2013) and tremendously enhanced signal intensity. It took only 3 min to finish analyzing a plasma sample, which can save much time in experimental studies with hundreds of samples, and it was faster than the UPLC-MS/MS method with a run-time of 5 min for determination of the four probe drugs (caffeine, tolbutamide, metoprolol and dapsone) in rat plasma reported in the literature (Liu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…High‐throughput screening techniques have helped in the evaluation of potential CYP450 inhibition during drug discovery and development (Qin et al , ). Early publications have described methods for the simultaneous determination of multiple probe drugs using HPLC (Jerdi et al , ; Yao et al , ; Johansson et al , ), LC‐MS/MS (Scott et al , ; Zhang et al , ; Yin et al ., ; He et al , ; Lad, ; Hu et al , ; Oh et al , ; Lee et al , ; Wang et al , ) and UPLC‐MS/MS (De Bock et al , ; Liu et al , ). In this study, we developed an ultra‐performance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) method for analysis of the six probe drugs in a single‐run process.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma by UPLC‐MS/MS and its application to cytochrome P450 activity study in rats

Wang

Zhang

et al. 2015

Biomedical Chromatography

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A specific ultra-performance liquid chromatography tandem mass spectrometry method is described for the simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma with diazepam as internal standard, which are the six probe drugs of the six cytochrome P450 isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19 and CYP2C9. Plasma samples were protein precipitated with acetonitrile. The chromatographic separation was achieved using a UPLC® BEH C18 column (2.1 × 100 mm, 1.7 µm). The mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. The triple quadrupole mass spectrometric detection was operated by multiple reaction monitoring in positive electrospray ionization. The precisions were <13%, and the accuracy ranged from 93.3 to 110.4%. The extraction efficiency was >90.5%, and the matrix effects ranged from 84.3 to 114.2%. The calibration curves in plasma were linear in the range of 2-2000 ng/mL, with correlation coefficient (r(2) ) >0.995. The method was successfully applied to pharmacokinetic studies of the six probe drugs of the six CYP450 isoforms and used to evaluate the effects of erlotinib on the activities of CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19 and CYP2C9 in rats. Erlotinib may inhibit the activity of CYP2B6 and CYP3A4, and may induce CYP2C9 of rats.

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“…However, few studies have examined CYP in NAFLD. In an animal model, CYP2E1 and 4A levels were found to be increased, [12,13] while CYP1A2 [14] and 2C11 [12] levels were decreased in the livers of rats with NAFLD. [14] In humans, a previous study reported that the expression of CYP2E1 was high in patients with NAFLD.…”

Section: Introductionmentioning

confidence: 87%

“…In an animal model, CYP2E1 and 4A levels were found to be increased, [12,13] while CYP1A2 [14] and 2C11 [12] levels were decreased in the livers of rats with NAFLD. [14] In humans, a previous study reported that the expression of CYP2E1 was high in patients with NAFLD. [15] Furthermore, microsomal CYP2A6, 2B6 and 2C9 mRNA expression levels were increased, whereas CYP1A2, 2D6 and 2E1 mRNA expression levels were decreased with the progression of NAFLD.…”

Section: Introductionmentioning

confidence: 87%

Diet-induced non-alcoholic fatty liver disease affects expression of major cytochrome P450 genes in a mouse model

Chiba

Noji

Shinozaki

et al. 2016

Journal of Pharmacy and Pharmacology

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Validated liquid chromatography–tandem mass spectrometry method for determination of totally nine probe metabolites of cytochrome P450 enzymes and UDP-glucuronosyltransferases

Cited by 14 publications

References 28 publications

Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

Simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma by UPLC‐MS/MS and its application to cytochrome P450 activity study in rats

Diet-induced non-alcoholic fatty liver disease affects expression of major cytochrome P450 genes in a mouse model

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