| Project/Area Number |
25670008
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Physical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
OE Tomoyuki 東北大学, 薬学研究科(研究院), 教授 (10203712)
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| Co-Investigator(Kenkyū-buntansha) |
GOTO Takaaki 東北大学, 大学院薬学研究科, 講師 (40344684)
LEE Seon Hwa 東北大学, 大学院薬学研究科, 助教 (60519776)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 反応性代謝物 / トラッピング試薬 / カクテル試薬 / 質量分析 |
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| Outline of Final Research Achievements |
Background・Aim: Reactive metabolites of drugs result in adverse drug reactions through the formation of covalent biding to biological macromolecules. Therefore, trapping assays, such as glutathione trapping method, are widely performed together with LC-MS for the screening. However, the current strategy still has problems: ex. low throughput, structural gap between trapping reagents and biological macromolecules, and metabolic degradation of the reagents. We therefore aimed to develop a high-throughput/hybrid screening system to solve the problems. Outcome: I) Using simple motif of each nucleophilic site followed by mixing as a cocktail, the structural gap and metabolic degradation were avoided. II) Concomitant use of the stable isotope labeled motifs facilitated the screening because of the characteristic doublet peaks. III) Isotope pattern dependent scanning enabled the automated MS/MS analysis using the characteristic doublet peaks.
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