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Search for hypnotic metabolites for forensic toxicological analysis

Research Project

Project/Area Number 16K09221
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Legal medicine
Research InstitutionNippon Medical School

Principal Investigator

Yamaguchi Koji  日本医科大学, 医学部, 講師 (90465344)

Project Period (FY) 2016-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords睡眠薬 / ゾルピデム / LC-MS/MS / 代謝 / 代謝物 / 定量分析 / 代謝物合成 / 有機合成 / 胆汁 / 水酸化体 / 合成 / 法医学 / 薬物代謝 / 有機化学 / 分析科学
Outline of Final Research Achievements

The aim of this study is to investigate metabolites of zolpidem (ZOL) in urines obtained from autopsies. The search for ZOL metabolites using LC-MS/MS revealed the presence of novel metabolites, 7-hydroxy ZOL (7-OH), 8-hydroxy ZOL (8-OH), ZOL dihydrodiol, and cysteine conjugates of ZOL, in urine.
ZOL metabolites, M1-4, 7-OH and 8-OH were synthesized. These products were used as authentic standards. And a method for simultaneous analysis of ZOL, M1-4, 7-OH, and 8-OH in urine was developed.
Quantitative analysis of ZOL and its metabolites in human urines revealed that concentrations of M1 was the highest, followed by those of M2, 7-OH, M4.

Academic Significance and Societal Importance of the Research Achievements

ヒトの資料を用い、日本で最も販売されているゾルピデムの代謝について研究した。得られた知見により、今後ゾルピデムが犯罪に悪用され、ゾルピデムが使用されたことを証明する時に、より証拠力の高い鑑定が可能になった。今後、ゾルピデムの排泄の経時変化が明らかになれば、服用時間のおおよその推定が可能になったり、事件から長時間経過していても尿からゾルピデム代謝物を検出できるようになる可能性がある。

Report

(6 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2021 2018 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Qualitative analysis of zolpidem and its metabolites M-1 to M-4 in human blood and urine using liquid chromatography-tandem mass spectrometry2021

    • Author(s)
      Yamaguchi Koji、Miyaguchi Hajime、Hirakawa Keiko、Ohno Youkichi、Kanawaku Yoshimasa
    • Journal Title

      Forensic Toxicology 134

      Volume: 39 Issue: 1 Pages: 134-145

    • DOI

      10.1007/s11419-020-00551-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 銅触媒による3成分カップリング反応を用いたゾルピデム代謝物の合成2018

    • Author(s)
      山口晃志、増田優紀、普神敬悟、石川慎吾、大野曜吉
    • Organizer
      日本法中毒学会第37年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Analysis of zolpidem metabolites in human bile: identification of hydroxyzolpidems by LC-MS/MS and chemical synthesis2016

    • Author(s)
      Koji Yamaguchi, Keigo Fugami, Shingo Ishikawa, Youkichi Ohno
    • Organizer
      The 54th annual meeting of the international association of forensic toxicology
    • Place of Presentation
      オーストラリア ブリスベン
    • Year and Date
      2016-08-28
    • Related Report
      2016 Research-status Report
  • [Presentation] 7-ヒドロキシゾルピデムの合成及び剖検で得られた胆汁からの検出2016

    • Author(s)
      山口晃志、普神敬悟、石川慎吾、大野曜吉
    • Organizer
      日本法中毒学会第35年会
    • Place of Presentation
      大阪
    • Year and Date
      2016-07-01
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-01-27  

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