Simultaneous LC-MS/MS Analysis of the Plasma Concentrations of a Cocktail of 5 Cytochrome P450 Substrate Drugs and Their Metabolites
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- Tanaka Shimako
- Department of Pharmacy Practice & Science, School of Pharmaceutical Sciences, University of Shizuoka
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- Uchida Shinya
- Department of Pharmacy Practice & Science, School of Pharmaceutical Sciences, University of Shizuoka
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- Inui Naoki
- Department of Clinical Pharmacology & Therapeutics, Hamamatsu University School of Medicine
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- Takeuchi Kazuhiko
- Department of Clinical Pharmacology & Therapeutics, Hamamatsu University School of Medicine
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- Watanabe Hiroshi
- Department of Clinical Pharmacology & Therapeutics, Hamamatsu University School of Medicine
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- Namiki Noriyuki
- Department of Pharmacy Practice & Science, School of Pharmaceutical Sciences, University of Shizuoka
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A “cocktail” approach, which involves simultaneous administration of multiple CYP-specific probes, concurrently detects the activity of multiple CYP enzymes. We developed and validated a rapid and selective LC-MS/MS method for determining the plasma concentrations of 5 CYP probe drugs and metabolites (caffeine/paraxanthine, CYP1A2 substrate; losartan/losartan carboxylic acid (E3174), CYP2C9 substrate; omeprazole/5-hydroxyomeprazole, CYP2C19 substrate; dextromethorphan/dextrorphan, CYP2D6 substrate; and midazolam/1′-hydroxymidazolam, CYP3A4 substrate) by single-step extraction, followed by a single LC-MS/MS run. An Ostro™ 96-well plate was used for extraction of CYP substrates and metabolites from human plasma and urine. Following optimization of the chromatographic conditions, all the peaks were well separated, and retention times ranged between 4.4 and 11.7 min. The total run time for a single injection was within 13 min. The accuracy and precision values suggested that the assay had high accuracy and reliability in plasma and urine samples. No significant matrix interference was observed. To demonstrate the efficacy of this method, plasma and urine concentrations of 5 CYP probe substrates and their metabolites were determined after simultaneous oral administration of 5 drugs to 4 healthy volunteers. All the substrates and metabolites were detected over an 8 h period, and the plasma concentrations of each substrate at 8 h after administration were above the lower limit of quantification. Urine concentrations of drugs and their metabolic ratio were evaluated after the administration. In conclusion, the advantage of our cocktail approach is that it enables in vivo assessment of the activity of various drug-metabolizing enzymes in a single assay.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 37 (1), 18-25, 2014
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204631699584
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- NII論文ID
- 130003382092
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC2czitFamsQ%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 025136467
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- PubMed
- 24389476
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可