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Direct quantification of toxic substances in frozen tissues by MALDI-MS/MS

Research Project

Project/Area Number 16K09206
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Legal medicine
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Minakata Kayoko  浜松医科大学, 医学部, 特任研究員 (70115509)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords質量分析 / 薬毒物 / 危険ドラッグ / 合成カンナビノイド / 代謝物 / 高感度分析 / 尿 / 高感度定量 / ジフェニジン / 凍結切片 / mass spectrometry / MALDI / 脂肪組織 / 標準添加法 / 社会医学 / 分析科学 / 薬学 / 有機化学
Outline of Final Research Achievements

The direct quantification method of toxic substances in tissues from a cadaver (intoxicated with diphenidine in this case) was devised. About 20 pieces of 20 μm-thick frozen tissue sections (5x5mm) were prepared. On a MALDI plate, standard solutions of diphenidine, tissue section and matrix were piled on successively, and diphenidine was quantified by MALDI-MS/MS using standard addition method. This result was reported in Forensic Toxicology 34:151, 2016. Much more sensitive method was required for the quantification of synthetic cannabinoids because they were metabolized very quickly and could not be determined by the previous methods in most cases. Our new method was devised based on liquid chromatography (LC)-QTRAP-MS/MS, and the LOQ of the method was 10 pg/mL (that is 1/100 of the LOQ in the previous reports). This method was applied successfully to several cases where toxic substances were unknown.

Academic Significance and Societal Importance of the Research Achievements

法医学や救急救命においては原因不明の中毒にしばしば遭遇し、薬毒物の迅速で信頼がおける分析が必要である。matrix assisted laser ionization (MALDI) tandem mass spectrometry (MS/MS) 法は試料をプレートに乗せ、装置に挿入すると20秒で結果が得られる迅速で高感度な質量分析法である。ヒト解剖組織の凍結切片にこの方法を適用することにより、ヒトにおける薬毒物の影響や組織中の局在箇所を特定するという学術的意義がある。薬毒物およびその代謝物の高感度で迅速な定量法を開発することにより中毒の原因解明という社会的意義がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (31 results)

All 2019 2018 2017 2016 Other

All Journal Article (13 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 13 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) (of which Int'l Joint Research: 6 results) Remarks (1 results)

  • [Journal Article] Sensitive quantification of BB-22 and its metabolite BB-22 3-carboxyindole, and characterization of new metabolites in authentic urine and/or serum specimens obtained from three individuals by LC-QTRAP-MS/MS and high-resolution LC-Orbitrap-MS/MS2019

    • Author(s)
      Kayoko Minakata, Koutaro Hasegawa, Hideki Nozawa, Itaru Yamagishi, Takeji Saitoh, Atsuto Yoshino, Masako Suzuki, Takuya Kitamoto, Osamu Suzuki, Kanako Watanabe
    • Journal Title

      Forensic Toxicology

      Volume: 37 Issue: 1 Pages: 164-173

    • DOI

      10.1007/s11419-018-0448-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sensitive quantification of 5F-NNEI and characterization of its several metabolites in authentic urine and/or serum specimens obtained from three individuals by LC-QTRAP-MS/MS and high-resolution LC-Orbitrap-MS/MS2018

    • Author(s)
      Kayoko Minakata, Hideki Nozawa, Itaru Yamagishi, Koutaro Hasegawa, Takeji Saitoh, Atsuto Yoshino, Masako Suzuki, Takuya Kitamoto, Osamu Suzuki, Kanako Watanabe
    • Journal Title

      Forensic Toxicology

      Volume: 36 Issue: 2 Pages: 498-505

    • DOI

      10.1007/s11419-018-0429-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and quantification of predominant metabolites of synthetic cannabinoid MAB-CHMINACA in an authentic human urine specimen.2018

    • Author(s)
      2.Hasegawa K, Minakata K, Gonmiri K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O
    • Journal Title

      Drug Testing and Analysis

      Volume: 10 Issue: 2 Pages: 365-371

    • DOI

      10.1002/dta.2220

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fatal zolpidem poisoning due to its intravenous self-injection: Post mortem distribution/redistribution of zolpidem and its predominant metabolite zolpidem phenyl-4-carboxylic acid in body fluids and solid tissues in an autopsy case2018

    • Author(s)
      Koutaro Hasegawa, Amin Wurita, Hideki Nozawa, Itaru Yamagishi, Kayoko Minakata, Kanako Watanabe, Osamu Suzuki
    • Journal Title

      Forensic Science International

      Volume: 290 Pages: 111-120

    • DOI

      10.1016/j.forsciint.2018.06.044

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A case of intoxication with a mixture of synthetic cannabinoids EAM-2201, AB-PINACA and AB-FUBINACA, and a synthetic cathinone α-PVP2018

    • Author(s)
      Itaru Yamagishi, Kayoko Minakata, Hideki Nozawa, Koutaro Hasegawa, Masako Suzuki, Takuya Kitamoto, Osamu Suzuki, Kanako Watanabe
    • Journal Title

      Legal Medicine

      Volume: 35 Pages: 44-49

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sensitive quantification of 5F-PB-22 and its three metabolites 5F-PB-22 3-carboxyindole, PB-22 N-5-hydroxypentyl and PB-22 N-pentanoic acid in authentic urine specimens obtained from four individuals by liquid chromatography-tandem mass spectrometry2018

    • Author(s)
      Kayoko Minakata, Koutaro Hasegawa, Itaru Yamagishi, Hideki Nozawa, Hanajiri RK, Masako Suzuki, Takuya Kitamoto, Osamu Suzuki, Kanako Watanabe
    • Journal Title

      Forensic Toxicology

      Volume: 36 Issue: 1 Pages: 151-159

    • DOI

      10.1007/s11419-017-0395-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Quantitation of biperiden in whole blood by MALDI-QTOF tandem mass spectrometry, and estimation of new metabolites in urine of deceased subjects treated with biperiden antemortem2017

    • Author(s)
      Minakata K, Yamagishi I, Nozawa H, Hasegawa K, Suzuki M, Gonmori K, Suuzuki O, Watanabe K
    • Journal Title

      Forensic Toxicology

      Volume: 35 Issue: 1 Pages: 86-93

    • DOI

      10.1007/s11419-016-0341-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sensitive identification and quantification of parent forms of six synthetic cannabinoids in urine samples of human cadavers by liquid chromatography-tandem mass spectrometry2017

    • Author(s)
      Minakata K, Yamagishi I, Nozawa H, Hasegawa K, Suzuki M, Gonmori K, Suuzuki O, Watanabe K
    • Journal Title

      Forensic Toxicology

      Volume: 印刷中 Issue: 2 Pages: 275-283

    • DOI

      10.1007/s11419-017-0354-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Semiquantitation of diphenidine in tissue sections obtained from a human cadaver in a poisoning case by direct MALDI-QTOF mass spectrometry2016

    • Author(s)
      Kayoko Minakata, Itaru Yamagishi, Hideki Nozawa, Koutaro Hasegawa, Kunio Gonmori, Masako Suzuki, Amin Wurita, Osamu Suzuki, Kanako Watanabe
    • Journal Title

      Forensic Toxicology

      Volume: 34 Issue: 1 Pages: 151-157

    • DOI

      10.1007/s11419-015-0300-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Postmortem redistribution of methamphetamine and amphetamine in blood specimens from various blood vessels and in the specimens from rericardial fluid, bile, stomach contents and various solid tissues collected from a human cadaver2016

    • Author(s)
      Amin W, Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Suzuki O, Watanabe K
    • Journal Title

      Forensic Toxicology

      Volume: 34 Issue: 1 Pages: 191-198

    • DOI

      10.1007/s11419-015-0303-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification and quantification of metabolites of AB-CHMINACA in a urine specimen of an abuser2016

    • Author(s)
      Amin Wurita, Koutaro Hasegawa, Kayoko Minakata, Kunio Gonmori, Hideki Nozawa, Itaru Yamagishi, Osamu Suzuki, Kanako Watanabe
    • Journal Title

      Legal Medicine

      Volume: 19 Pages: 113-118

    • DOI

      10.1016/j.legalmed.2015.07.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Simultaneous determination of cyclic antidepressants and their related drugs and the estimation of new metabolites in human whole blood and urine by MALDI-QTOF-mass spectrometry2016

    • Author(s)
      Nozawa H, Minakata K, Yamagishi I, Hasegawa K, Suzuki M, Gonmori K, Suzuki O, Watanabe K
    • Journal Title

      Forensic Toxicology

      Volume: 34 Issue: 2 Pages: 244-255

    • DOI

      10.1007/s11419-016-0313-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Application of MALDI-QTOF mass spectrometry to the determination of timiperone in whole blood, and estimation of its new metabolites in urine of a deceased subject who had been treated timiperone antemortem2016

    • Author(s)
      Nozawa H, Minakata K, Yamagishi I, Hasegawa K, Suzuki M, Gonmori K, Suzuki O, Watanabe K
    • Journal Title

      Forensic Toxicology

      Volume: 34 Issue: 2 Pages: 363-371

    • DOI

      10.1007/s11419-016-0323-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Analysis of new metabolites of biperiden in blood and urine of two deceased subjects having a history of its treatments2018

    • Author(s)
      Kayoko Minakata, Hideki Nozawa, Itaru Yamagishi, Koutaro Hasegawa, Amin Wurita, Osamu Suzuki, Kanako Watanabe
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Determination of timiperone in blood and estimation of its new metabolites in urine of a deceased2018

    • Author(s)
      Hideki Nozawa, Kayoko Minakata, Itaru Yamagishi, Koutaro Hasegawa, Amin Wurita, Osamu Suzuki, Kanako Watanabe
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A case of intoxication with a mixture of synthetic cannabinoids EAM-2201, AB-PINACA and AB-FUBINACA, and a synthetic cathinone α-PVP2018

    • Author(s)
      Itaru Yamagishi, Kayoko Minakata, Hideki Nozawa, Koutaro Hasegawa, Masako Suzuki, Takuya Kitamoto, Osamu Suzuki, Kanako Watanabe
    • Organizer
      24th Congress of the International Academy of Legal Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 4名の尿中5F-PB-22とその3種の代謝物(5F-PB-22 3-carboxyindole, PB-22 N-5-hydroxypentyl, PB-22 N-pentanoic acid)のLC-MS/MSによる高感度分析2018

    • Author(s)
      南方かよ子、長谷川弘太郎、山岸格、野澤秀樹、花尻(木倉)瑠理、阿民勿日他、権守邦夫、鈴木修、渡部加奈子
    • Organizer
      日本法中毒学会第37年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification and quantification of synthetic cannabinoid 5F-ADB-PINACA and its predominant metabolites in an authentic human urine specimen2018

    • Author(s)
      Koutaro Hasegawa, Amin Wurita, Kayoko Minakata, Hideki Nozawa, Itaru Yamagishi, Kanako Watanabe, Osamu Suzuki,
    • Organizer
      TIAFT2018 the International Associationof Forensic Toxicologist
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] LC-QTRAP-MS/MSとLC-Orbitrap-MS/MSを用いた3名の血清・尿中の合成カンナビノイド5F-NNEIの定量とその代謝物の構造推定2018

    • Author(s)
      南方かよ子、鈴木雅子、北本卓也、野澤秀樹、山岸格、長谷川弘太郎、齊藤岳児、吉野篤人、鈴木修、渡部加奈子
    • Organizer
      第43回日本医用マススペクトル学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マトリックス支援レーザー脱離イオン化(MALDI)MS/MSを用いたチミペロンの定量と新しい代謝物の推定2017

    • Author(s)
      野澤秀樹、南方かよ子、山岸格、長谷川弘太郎、権守邦夫、鈴木修、渡部加奈子
    • Organizer
      第101次日本法医学会学術全国集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト尿中からの合成カンナビノイドMAB-CHMINACAの代謝物の同定と定量2017

    • Author(s)
      長谷川弘太郎、南方かよ子、権守邦夫、野澤秀樹、山岸格、渡部加奈子、鈴木修
    • Organizer
      日本法中毒学会第36年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 3剖検尿から検出された6種の合成カンナビノイドのLC-MS/MSによる高感度分析2017

    • Author(s)
      南方かよ子、山岸格、野澤秀樹、長谷川弘太郎、権守邦夫、鈴木修、渡部加奈子
    • Organizer
      日本法中毒学会第36年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 血液・組織中の合成カンナビノイド・合成カチノンのLC-QTRAP MS/MSによる高感度分析2017

    • Author(s)
      南方かよ子、鈴木雅子、北本卓也、山岸格、野澤秀樹、長谷川弘太郎、鈴木修、渡部加奈子
    • Organizer
      第42回日本医用マススペクトル学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト尿中からの合成カンナビノイド5F-ADB-PINACA代謝物の検出2017

    • Author(s)
      長谷川弘太郎、南方かよ子、権守邦夫、野澤秀樹、山岸格、渡部加奈子、鈴木修
    • Organizer
      第39回日本法医学会学術中部地方集会
    • Related Report
      2017 Research-status Report
  • [Presentation] ビペリデン代謝物のMALDI-QTOF-MSによる分析2016

    • Author(s)
      南方かよ子、鈴木雅子、野澤秀樹、山岸格、長谷川弘太郎、権守邦夫、鈴木修、渡部加奈子
    • Organizer
      第41回日本医用マススペクトル学会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-09-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Diphenidine and its metabolites in blood and urine analyzed by matrix-assisted laser desorption ionization quadrupole time-of-flight mass spectrometry2016

    • Author(s)
      Kayako Minakata, Itaru Yamagishi, Hideki Nozawa, Koutaro Hasegawa, Kunio Gonmori, Osamu Suzuki, Kanako Watanabe
    • Organizer
      54th Annual meeting of the International Association of Forensic Toxicologists (TIAFT)
    • Place of Presentation
      Brisbane, Australia
    • Year and Date
      2016-08-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification and quantifiation of metabolites of AB-CHMINACA in a urine specimen of an abuser2016

    • Author(s)
      Koutaro Hasegawa, Amin Wurita, Kayako Minakata, Kunio Gonmori, Hideki Nozawa, Itaru Yamagishi, Osamu Suzuki, Kanako Watanabe
    • Organizer
      54th Annual meeting of the International Association of Forensic Toxicologists (TIAFT)
    • Place of Presentation
      Brisbane, Australia
    • Year and Date
      2016-08-28
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 解剖事例におけるメタンフェタミンとアンフェタミンの臓器・体液での再分布の検討2016

    • Author(s)
      長谷川弘太郎、阿民勿日他、南方かよ子、権守邦夫、野澤秀樹、山岸格、鈴木修、渡部加奈子
    • 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
  • [Presentation] 血液中の抗パーキンソン病薬のマトリックス支援レーザー脱離イオン化(MALDI)MS/MSを用いた定量法2016

    • Author(s)
      南方かよ子、山岸格、野澤秀樹、長谷川弘太郎、権守邦夫、鈴木修、渡部加奈子
    • Organizer
      第100次日本法医学会学術全国集会
    • Place of Presentation
      東京
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
  • [Presentation] 数種の危険ドラッグが死亡に関与している可能性がある1剖検例2016

    • Author(s)
      山岸格、南方かよ子、野澤秀樹、長谷川弘太郎、権守邦夫、鈴木修、渡部加奈子
    • Organizer
      第38回日本法医学会学術中部地方会
    • Place of Presentation
      福井
    • Related Report
      2016 Research-status Report
  • [Remarks] HamaMed-Repository

    • URL

      http://hikumano.hama-med.ac.jp/dspace/

    • Related Report
      2018 Annual Research Report 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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