2022 Fiscal Year Final Research Report
Construction and verification of a database library of drugs and metabolites detected in formalin tissues and fixatives utilizing in silico analysis
| Project/Area Number |
17K09279
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
UEKUSA Kyoko 日本医科大学, 医学部, マネジメントサポート・スタッフ (50409215)
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| Co-Investigator(Kenkyū-buntansha) |
石野 孔祐 日本医科大学, 医学部, 講師 (60584878)
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| Project Period (FY) |
2017-04-01 – 2023-03-31
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| Keywords | ホルマリン保存 / 代謝物解析 / Q-TOF / クエチアピン / S酸化 / 酸素付加体 |
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| Outline of Final Research Achievements |
To enhance the analysis of drugs in tissues following formalin fixation, using Q-TOF analysis software, we constructed a database library of drugs, metabolites, and other compounds detected in formalin-fixed liver and fixative.Existing Q-TOF data for fixed liver tissues from drug-positive cases were analyzed in silico to predict metabolites using ACD/Meta Sense software. Four predicted metabolites were newly used as standards for verification of unidentifiable compounds registered as estimations in Personal Compound Database Library(PCDL).Using updated PCDL, a drug and metabolite search was performed with the previous Q-TOF data. This search returned good library search scores.The predicted three types of quetiapine were identified from the product ion spectrum.
This study demonstrated the feasibility of constructing a database library to search for drugs and metabolites in formalin-fixed tissues via in silico analysis incorporating updated Q-TOF data for metabolites.
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| Free Research Field |
法医中毒学
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト臓器中の法医薬毒物分析は解剖直後あるいは凍結保存した組織などで実施するのが通例であるが剖検時に薬物使用が疑われず、その後の捜査等で薬物の関与が判明し長期間経過後に薬物分析検査やその分析結果の解釈について意見を求められる場合がある。ホルマリン臓器中の薬物分析では臓器と保存液の保存期間や代謝物をも鑑みた分析が重要である。本研究ではQ-TOF分析・解析ソフトにより薬物と代謝物の検索を実施した。In silico 解析を活用し代謝物のQ-TOFデータの更新と抽出法改良によってホルマリン臓器中の薬物および代謝物の検索により有用なデータベースライブラリの構築が可能であり、法医実試料への適用を目指す。
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