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Development of a highly sensitive analytical method for nerve agent degradation products in biological samples

Research Project

Project/Area Number 19K16364
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
Research InstitutionNational Research Institute of Police Science

Principal Investigator

Yamaguchi Akinori  科学警察研究所, 法科学第三部, 研究員 (50822087)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords神経剤 / LC-MS / ノビチョク / 誘導体化 / DMTMM / リン酸 / DABCO / 加水分解物 / RMPA / LC/MS / 縮合剤 / 活性エステル / 生体試料 / LC-MS/MS / 未知物質の構造推定
Outline of Research at the Start

本研究では、神経剤加水分解生成物をより温和な条件で誘導体化し、さらに分析対象の疎水性やイオン化効率を向上させるトリアジン型のベンジル化剤等を用いる新規誘導体化反応の開発と、その手法を利用したLC-MS/MSによる神経剤分解物の高感度検知・同定手法の確立を目的とする。

Outline of Final Research Achievements

Analytical methods for detecting the use of nerve agents from biological samples are inadequate, especially for the new Novichok nerve agents that have not yet been reported. The principal investigator has developed an analytical method for the degradation products of Novichok-A agents and conventional nerve agent degradation products, RMPAs, using the condensing agent DMTMM and LC-MS/MS. This method uses DMTMM to convert Novichok-A agent degradation products into stable esters that can be detected by LC-MS/MS. Using this method, an analytical method for Novichok degradation products in urine was also realized; although the detection limit of RMPA is comparable to that of conventional methods, highly sensitive analysis of Novichok degradation products has been very difficult. This method is inexpensive, uses general-purpose equipment, and can be easily implemented in many laboratories.

Academic Significance and Societal Importance of the Research Achievements

研究代表者は新たな神経剤ノビチョクA剤の加水分解物の初めての分析法を開発しました。この分析法は、従来の神経剤分解物に対しても、従来法と同等または優れた性能を示します。本法に必要な設備は、一般的なLC-MS装置と安価な市販試薬のみであるため、リソースに限りのある研究室でも実施可能です。
本法を用いることで、生体試料に対しても高感度な分析が可能であり、このことは化学テロに対する迅速かつ正確な対応に資することを意味します。ノビチョクを含む神経剤は極めて危険な化学兵器であるため、その対応力を増強する本法の開発は公共の安全と国際的な安全保障の観点から重要です。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Dimethoxytriadinylation LC-MS/MS of Novichok A-Series Degradation Products in Human Urine2022

    • Author(s)
      Akinori Yamaguchi, Hajime Miyaguchi, Manabu Tokeshi
    • Journal Title

      Analytical Chemistry

      Volume: 94 Issue: 11 Pages: 4658-4665

    • DOI

      10.1021/acs.analchem.1c04634

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of degradation products of Novichok agents in human urine by hydrophilic interaction liquid chromatography-tandem mass spectrometry2022

    • Author(s)
      Otsuka Mai、Yamaguchi Akinori、Miyaguchi Hajime
    • Journal Title

      Forensic Toxicology

      Volume: - Issue: 2 Pages: 0-0

    • DOI

      10.1007/s11419-022-00656-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ノビチョクを含む神経剤加水分解物のジメトキシトリアジニル (DMT) 誘導体化LC?MS/MS法の開発2022

    • Author(s)
      山口晃巨, 宮口一
    • Organizer
      第29回クロマトグラフィーシンポジウム
    • Related Report
      2022 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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