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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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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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 / 代謝物予測 / LC-QTOF / データベースライブラリ / QTOF / データベース構築 / QTOF-LC/MS / GC/MS / S酸化物 / 法医中毒学 / GC-MS |
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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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| 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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Report
(7 results)
Research Products
(19 results)
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[Journal Article] DNA Adductome Analysis Identifies N-Nitrosopiperidine Involved in the Etiology of Esophageal Cancer in Cixian, China2019
Author(s)
Totsuka Y, Lin Y, He Y, Ishino K, Sato H, Kato M, Nagai M, Elzawahry A, Totoki Y, Nakamura H, Hosoda F, Shibata T, Matsuda T, Matsushima Y, Song G, Meng F, Li D, Liu J, Qiao Y, Wei W, Inoue M, Kikuchi S, Nakagama H, Shan B
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Journal Title
Chemical Research in Toxicology
Volume: 32
Issue: 8
Pages: 1515-1527
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Downregulation of protein disulfide-isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma2019
Author(s)
Kondo R, Ishino K, Wada R, Takata H, Peng WX, Kudo M, Kure S, Kaneya Y, Taniai N, Yoshida H, Naito Z
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Journal Title
International Journal of Oncology
Volume: 54
Pages: 1409-1421
DOI
Related Report
Peer Reviewed
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[Journal Article] 2-Deoxy-D-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells2018
Author(s)
Ishino K, Kudo M, Peng WX, Kure S, Kawahara K, Teduka K, Kawamoto Y, Kitamura T, Fujii T, Yamamoto T, Wada R, Naito Z
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Journal Title
Biochem Biophys Res Comm
Volume: 501
Issue: 3
Pages: 668-673
DOI
Related Report
Peer Reviewed / Open Access
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