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Development of enhanced throughput LC/MS assays of steroid hormones based on sample and analyte-multiplexing

Research Project

Project/Area Number 20K06990
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionTokyo University of Science

Principal Investigator

Higashi Tatsuya  東京理科大学, 薬学部薬学科, 教授 (90272963)

Co-Investigator(Kenkyū-buntansha) 石毛 崇之  千葉大学, 医学部附属病院, 臨床検査技師 (30757315)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords検体・項目多重化 / ハイスループット / ステロイドホルモン / LC/MS / 臨床検査 / 誘導体化 / MSタグ / 骨粗鬆症 / エストラジオール / ビタミンD / 原発性アルドステロン症 / 加齢男性性腺低下症候群
Outline of Research at the Start

様々な内分泌系疾患のステロイドホルモン検査において,複数の検体 (同一被検者から採取した複数検体あるいは異なる被検者の検体) を一括で,しかも正診率を向上させるために複数の関連ステロイドを同時に測定できる,ハイスループットかつ,LC/MS (高速液体クロマトグラフィー/質量分析法) を基盤とする精度の高い手法を確立する.これを実現するうえでの鍵は,測定対象にタグをつけて一度の測定で扱える検体と項目 (ステロイドホルモン) を増やすことであり,本研究ではこれをSample and Analyte-Multiplexing = SAM技術と呼び,これを開発する.

Outline of Final Research Achievements

The novel methods employing multiple MS tags, named as “SAM (Sample and Analyte-Multiplexing)”, were proposed and developed to enhance the throughput of the LC/MS-based tests for some steroid hormones, which are currently used as the diagnostic and therapeutic markers for primary aldosteronism, late-onset hypogonadism syndrome and osteoporosis. By the SAM methods, the total LC/MS run times were reduced by up to 60%, compared with those in the previous methods. Furthermore, the newly developed methods enabled the simultaneous measurements of two steroid hormones which are hitherto measured by the two separate methods; this capability further enhanced the assay throughput.

Academic Significance and Societal Importance of the Research Achievements

本研究により,ステロイドホルモンのLC/MS検査の実用化を阻んでいる「スループットの低さ」が,適切にデザインされたMSタグを利用する「検体・項目多重化 (SAM) 技術」によって克服できることが示された.すなわち,本成果は各病院・検査機関が現有するLC/MS装置でも検査のハイスループット化が可能であることを証明しており,ステロイドホルモン検査には正診度及び医療経済性に優れるLC/MSを第一手法とすべきことを強く提言するものである.

Report

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

    (15 results)

All 2022 2021 2020

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] An LC/ESI-MS/MS Method for Quantification of Hexanoylglycine in Three Different Urine Samples Within a Single Run Using Triplex 1-[(4- Diethylaminophenyl)carbonyl]piperazine Isotopologues2022

    • Author(s)
      Hobo Wataru, Jo Akihiro, Koyagi Sae, Ogawa Shoujiro, Nishimoto-Kusunose Shoichi, Higashi Tatsuya
    • Journal Title

      CHROMATOGRAPHY

      Volume: 43 Issue: 3 Pages: 111-117

    • DOI

      10.15583/jpchrom.2022.010

    • ISSN
      1342-8284, 1348-3315
    • Year and Date
      2022-10-20
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of 4-Diethylaminobenzoic Acid <i>N</i>-Succinimidyl Ester and Its Deuterated Isotopologue as Derivatization Reagents to Quantitative Analysis of γ-Aminobutyric Acid in Serum by LC/ESI-MS/MS2022

    • Author(s)
      Mikami Yohei, Aizawa Mizuo, TodaA Ryoko, Ogawa Shoujiro, Nishimoto-Kusunose Shoichi, Ishige Takayuki, Higashi Tatsuya
    • Journal Title

      CHROMATOGRAPHY

      Volume: 43 Issue: 2 Pages: 53-58

    • DOI

      10.15583/jpchrom.2022.004

    • ISSN
      1342-8284, 1348-3315
    • Year and Date
      2022-06-20
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A method for determination of aldosterone concentrations of six adrenal venous serum samples during a single LC/ESI-MS/MS run using a sextet of Girard reagents2022

    • Author(s)
      Ohta Arisa, Hobo Wataru, Ogawa Shoujiro, Sugiura Yuki, Nishikawa Tetsuo, Nishimoto Koshiro, Nishimoto-Kusunose Shoichi, Higashi Tatsuya
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 207 Pages: 114423-114423

    • DOI

      10.1016/j.jpba.2021.114423

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] An LC/MS/MS Method for Quantifying Testosterone and Dehydroepiandrosterone Sulfate in Four Different Serum Samples during a Single Run2021

    • Author(s)
      Fujimura Shunsuke, Ito Takenori, Ogawa Shoujiro, Ishige Takayuki, Nishimoto-Kusunose Shoichi, Higashi Tatsuya
    • Journal Title

      Analytical Sciences

      Volume: advpub Issue: 0 Pages: 167-173

    • DOI

      10.2116/analsci.21P268

    • NAID

      130008095460

    • ISSN
      0910-6340, 1348-2246
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancing LC/ESI-MS/MS Throughput for Plasma Bile Acid Assay by Derivatization-based Sample-Multiplexing2020

    • Author(s)
      Jo Akihiro,Koyagi Sae,Hobo Wataru,Otani Saori,Ogawa Shoujiro,Higashi Tatsuya
    • Journal Title

      Analytical Sciences

      Volume: 36 Issue: 9 Pages: 1099-1104

    • DOI

      10.2116/analsci.20P082

    • NAID

      130007898806

    • ISSN
      0910-6340, 1348-2246
    • Year and Date
      2020-09-10
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derivatization‐based quadruplex LC/ESI?MS/MS method for high throughput quantification of serum dehydroepiandrosterone sulfate2020

    • Author(s)
      Aso Saki、Ogawa Shoujiro、Nishimoto‐Kusunose Shoichi、Satoh Mamoru、Ishige Takayuki、Nomura Fumio、Higashi Tatsuya
    • Journal Title

      Biomedical Chromatography

      Volume: 35 Issue: 4

    • DOI

      10.1002/bmc.5027

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sample-multiplexing by derivatization using multiple analogous reagents for enhancing throughput in LC/ESI-MS/MS assay of steroids: Plasma 17α-hydroxyprogesterone as an example2020

    • Author(s)
      Kamemura Miki,Yokota Mai,Ogawa Shoujiro,Sugiura Takahiro,Higashi Tatsuya
    • Journal Title

      Journal of Chromatography B

      Volume: 1146 Pages: 122117-122117

    • DOI

      10.1016/j.jchromb.2020.122117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Derivatization-based sample-multiplexing for enhancing throughput in liquid chromatography/tandem mass spectrometry quantification of metabolites: an overview2020

    • Author(s)
      Higashi Tatsuya,Ogawa Shoujiro
    • Journal Title

      Journal of Chromatography A

      Volume: 1634 Pages: 461679-461679

    • DOI

      10.1016/j.chroma.2020.461679

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] DEAPPZアイソトポログ誘導体化による尿中hexanoylglycineの3検体一括LC/ESI-MS/MS定量法の開発2021

    • Author(s)
      帆保 航,城 彰宏,小八木冴,小川祥二郎,楠瀬翔一,東 達也
    • Organizer
      第33回バイオメディカル分析科学シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 6種のGirard試薬を用いた副腎静脈血清中アルドステロンの6検体一括LC/ESI-MS/MS定量法の開発2021

    • Author(s)
      太田有紗,帆保 航,水元優花,楠瀬翔一,小川祥二郎,杉浦悠毅,西本紘嗣郎,東 達也
    • Organizer
      第46回日本医用マススペクトル学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] DEAPPZアイソトポログを用いるhexanoylglycineの尿3検体一括LC/ESI-MS/MS定量法2021

    • Author(s)
      帆保 航,城 彰宏,小八木冴,小川祥二郎,楠瀬翔一,東 達也
    • Organizer
      第32回クロマトグラフィー科学会議
    • Related Report
      2021 Research-status Report
  • [Presentation] Enhancing sensitivity, specificity and analysis throughput for LC/ESI-MS/MS assessment of vitamin D status by derivatization with DAPTAD2021

    • Author(s)
      Tatsuya Higashi
    • Organizer
      31st International Symposium on Pharmaceutical and Biomedical Analysis (PBA2021)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Girard試薬アナログ及びアイソトポログを用いた血清中DHEASの4検体一括LC/MS/MS定量2020

    • Author(s)
      東 達也,麻生早希,小川祥二郎,佐藤 守,石毛崇之,野村文夫
    • Organizer
      日本臨床化学会第60回年次学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 2種のGirard試薬とそれらのアイソトポログを用いる血清中アンドロゲンの4検体一活LC/ESI-MS/MS定量法の開発2020

    • Author(s)
      藤村俊輔,伊藤孟徳,小川祥二郎,東 達也
    • Organizer
      第31回クロマトグラフィー科学会議
    • Related Report
      2020 Research-status Report
  • [Presentation] 6種のGirard型試薬を用いた副腎静脈血清中アルドステロンの6検体一括LC/ESI-MS/MS定量法の開発2020

    • Author(s)
      帆保 航,小八木 冴,太田有紗,楠瀬翔一,小川祥二郎,杉浦悠毅,東 達也
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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