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Development of derivatization procedures using reagent analogues and isotopologues for enhancing throughput of mass spectrometry-based clinical examinations

Research Project

Project/Area Number 17K08250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
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) 佐藤 守  千葉大学, 医学部附属病院, 特任准教授 (20401002)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords臨床検査 / 質量分析 / ハイスループット / 誘導体化 / アナログ / アイソトポログ / 多検体一括 / バイオマーカー / 分析科学 / LC/ESI-MS/MS / ハイスループット化 / 17α-ヒドロキシプロゲステロン / 副腎過形成症 / グルタル酸血症 / アナログ/アイソトポログ / 原発性アルドステロン症 / HPA軸 / 25-ヒドロキシビタミンD3 / ビタミンD欠乏症
Outline of Final Research Achievements

Mass spectrometry (MS) is accurate and economically-efficient methodology for clinical examinations, but its throughput is poor. This disadvantage deters the introduction of MS to the clinical practice. In this study, novel sample-multiplexed methods using sets of derivatization regent analogues and/or isotopologues were designed and developed to enhance the throughput of the MS-based clinical examinations for several diseases, such as vitamin D deficiency, estrogen-dependent cancer and primary aldosteronism. The developed methods could significantly reduce the analysis time (up to 60% less, compared with the conventional assays); thus the methods had a satisfactory applicability.

Academic Significance and Societal Importance of the Research Achievements

本研究により,MS臨床検査の最大の弱点であるスループットの低さが,適切にデザインされた誘導体化を基盤とする多検体一括定量,すなわち化学的アプローチによって克服できることが証明された.本成果は,各病院・検査機関が現有する装置を用いてハイスループットMS臨床検査が可能であることを意味しており,同時に検査手法がイムノアッセイから,正診度・医療経済性に優れるMSへと移行する流れを加速させるものと考えられる.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (25 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Quantitative MALDI-MS/MS assay for serum cortisol through charged derivatization2020

    • Author(s)
      Nakamura Masahiro、Moritsuna Marina、Yuda Keita、Fujimura Shunsuke、Sugiura Yuki、Shimma Shuichi、Nishimoto Koshiro、Nishikawa Tetsuo、Suematsu Makoto、Ogawa Shoujiro、Higashi Tatsuya
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 178 Pages: 112912-112912

    • DOI

      10.1016/j.jpba.2019.112912

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] (S)-1-(1-Methylpyridin-2-yl)-3-aminopiperidine as a novel derivatization reagent capable of enantiomeric separation and enhanced ESI-MS/MS detection for chiral carboxylic acids2019

    • Author(s)
      Matsumoto Takaaki,Sato Maho,Yamazaki Wataru,Ogawa Shoujiro,Higashi Tatsuya
    • Journal Title

      Microchemical Journal

      Volume: 146 Pages: 25-33

    • DOI

      10.1016/j.microc.2018.12.058

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of conjugation positions of urinary glucuronidated vitamin D 3 metabolites by LC/ESI‐MS/MS after conversion to MS/MS‐fragmentable derivatives2019

    • Author(s)
      Yoshimura Yusuke、Hibi Ryuichiro、Nakata Akiho、Togashi Moeka、Ogawa Shoujiro、Ishige Takayuki、Satoh Mamoru、Nomura Fumio、Higashi Tatsuya
    • Journal Title

      Biomedical Chromatography

      Volume: - Issue: 7

    • DOI

      10.1002/bmc.4538

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Method for Quantification of Tetrahydroglucocorticoid Glucuronides in Human Urine by LC/MS/MS with Isotope-coded Derivatization2018

    • Author(s)
      Matsumoto Takaaki, Yamazaki Wataru, Jo Akihiro, Ogawa Shoujiro, Mitamura Kuniko, Ikegawa Shigeo, Higashi Tatsuya
    • Journal Title

      Analytical Sciences

      Volume: 34 Issue: 9 Pages: 1003-1009

    • DOI

      10.2116/analsci.18SCP02

    • NAID

      130007474713

    • ISSN
      0910-6340, 1348-2246
    • Year and Date
      2018-09-10
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A method for determination of aldosterone in adrenal tributary venous serum by derivatization using Girard P reagent isotopologues followed by LC/ESI-MS/MS2018

    • Author(s)
      Higashi Tatsuya, Akaishi Miho, Yokota Mai, Suzuki Tatsunori, Ogawa Shoujiro, Sugiura Yuki, Nishikawa Tetsuo, Nishimoto Koshiro, Suematsu Makoto
    • Journal Title

      Journal of Chromatography B

      Volume: 1092 Pages: 106-113

    • DOI

      10.1016/j.jchromb.2018.06.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aldosterone and 18-oxocortisol coaccumulation in aldosterone-producing lesions2018

    • Author(s)
      Sugiura Yuki, Takeo Emi, Shimma Shuichi, Yokota Mai, Higashi Tatsuya, Seki Tsugio, Mizuno Yosuke, Oya Mototsugu Kosaka Takeo, Omura Masao, Nishikawa Tetsuo, Suematsu Makoto, Nishimoto Koshiro
    • Journal Title

      Hypertension

      Volume: 72 Issue: 6 Pages: 1345-1354

    • DOI

      10.1161/hypertensionaha.118.11243

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancing analysis throughput, sensitivity and specificity in LC/ESI-MS/MS assay of plasma 25-hydroxyvitamin D3 by derivatization with triplex DAPTAD isotopologues2017

    • Author(s)
      S. Ogawa, H. Kittaka, A. Nakata, M. Satoh, F. Nomura, T. Higashi
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 136 Pages: 126-133

    • DOI

      10.1016/j.jpba.2016.11.030

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Unconjugated bile acids in rat brain: Analytical method based on LC/ESI-MS/MS with chemical derivatization and estimation of their origin by comparison to serum levels2017

    • Author(s)
      Higashi Tatsuya, Watanabe Shui, Tomaru Koki, Yamazaki Wataru, Yoshizawa Kazumi, Ogawa Shoujiro, Nagao Hidenori, Minato Kouichi, Maekawa Masamitsu, Mano Nariyasu
    • Journal Title

      Steroids

      Volume: 125 Pages: 107-113

    • DOI

      10.1016/j.steroids.2017.07.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isotope-coded derivatization based LC/ESI-MS/MS methods using a pair of novel reagents for quantification of hydroxycinnamic acids and hydroxybenzoic acids in fermented brown rice product2017

    • Author(s)
      Ogawa Shoujiro, Takafuji Kiriko, Tsubuku Sumi, Horie Yukiko, Ikegawa Shigeo, Higashi Tatsuya
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 142 Pages: 162-170

    • DOI

      10.1016/j.jpba.2017.04.035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improved sensitivity of serum/plasma 1α,25-dihydroxyvitamin D quantification by DAPTAD derivatization2017

    • Author(s)
      Ishige Takayuki, Satoh Mamoru, Ogawa Shoujiro, Nishimura Motoi, Matsushita Kazuyuki, Higashi Tatsuya, Nomura Fumio
    • Journal Title

      Clinica Chimica Acta

      Volume: 473 Pages: 173-179

    • DOI

      10.1016/j.cca.2017.08.033

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 4種のGirard型試薬を用いた血漿中17α-hydroxyprogesteroneの4検体一括LC/ESI-MS/MS定量法2020

    • Author(s)
      亀村美樹,小川祥二郎,東 達也
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MPAPp:光学活性カルボン酸のLC/ESI-MS/MS用荷電誘導体化試薬の開発と評価2019

    • Author(s)
      松本孝彬,小川祥二郎,東 達也
    • Organizer
      第26回クロマトグラフィーシンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 荷電誘導体化を用いた血清中cortisolのMALDI-MS/MS定量法の開発2019

    • Author(s)
      藤村俊輔,森綱茉里奈,中村将大,小川祥二郎,杉浦悠毅,新間秀一,東 達也
    • Organizer
      第32回バイオメディカル分析科学シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 誘導体化-LC/ESI-MS/MSによる麹中エルゴチオネイン定量法の開発2019

    • Author(s)
      堀江裕紀子,後藤綺花,今村梨子,伊藤麻里,池川繁男,小川祥二郎,東 達也
    • Organizer
      日本分析化学会第68年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規LC/ESI-MS/MS定量法による3種の麹のエルゴチオネイン含量測定2019

    • Author(s)
      堀江裕紀子,後藤綺花,今村梨子,伊藤麻里,池川繁男,小川祥二郎,東 達也
    • Organizer
      第71回生物工学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 化学的手法とLC/ESI-MS/MSを組み合わせた,尿中グルクロン酸抱合型ビタミンD3代謝物の同定2019

    • Author(s)
      吉村友佑,冨樫萌香,小川祥二郎,東 達也
    • Organizer
      日本臨床化学会第59回年次学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 質量分析による主要なビタミンD代謝物の一斉定量への挑戦2019

    • Author(s)
      石毛崇之,佐藤 守,小川祥二郎,西村 基,川崎健治,松下一之,東 達也,野村文夫
    • Organizer
      日本臨床化学会第59回年次学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] DAPTAD誘導体化:LC/MSによる新生児のビタミンD供給状態評価の質を向上させる2019

    • Author(s)
      東 達也
    • Organizer
      日本分析化学会中部支部 静岡地区講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Development of LC/ESI-MS/MS method combined with derivatization for determination of L-ergothioneine in Aspergillus oryzae-fermented products of rice and rice bran2019

    • Author(s)
      Yukiko Horie, Ayaka Goto, Riko Imamura, Mari Itoh, Shigeo Ikegawa, Shoujiro Ogawa, Tatsuya Higashi
    • Organizer
      HPLC Kyoto - The 49th International Symposium on High Performance Liquid Phase Separations and Related Techniques
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MALDI/TOF-MS(/MS)によるステロイド定量法の開発2018

    • Author(s)
      中村将大,森綱茉里奈,湯田啓太,堀江裕紀子,小川祥二郎,杉浦悠毅,東 達也
    • Organizer
      第31回バイオメディカル分析科学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] LC/MS/MSによる血清/血漿1α,25-ジヒドロキシビタミンD定量および分析前変動要因の評価2018

    • Author(s)
      石毛崇之,佐藤 守,小川祥二郎,西村 基,松下一之,東 達也,野村文夫
    • Organizer
      第43回日本医用マススペクトル学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 4種のGirard試薬アナログを用いた誘導体化によるステロイドのハイスループットLC/ESI-MS/MS定量法の開発2018

    • Author(s)
      亀村美樹,横田麻衣,小川祥二郎,東 達也
    • Organizer
      第43回日本医用マススペクトル学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Girard試薬Pアイソトポログを用いた副腎静脈血清中アルドステロンのLC/ESI-MS/MS定量法2018

    • Author(s)
      赤石美帆,横田麻衣,小川祥二郎,杉浦悠毅,西川哲男,西本紘嗣郎,東 達也
    • Organizer
      第43回日本医用マススペクトル学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] DAPPZアイソトポログを用いる血漿中胆汁酸の3検体一括LC/ESI-MS/MS定量法の開発2018

    • Author(s)
      城 彰宏,大谷彩織,小川祥二郎,東 達也
    • Organizer
      第29回クロマトグラフィー科学会議
    • Related Report
      2018 Research-status Report
  • [Presentation] Girard 試薬アナログを用いるステロイドのハイスループットLC/ESI-MS/MS定量法の開発2018

    • Author(s)
      亀村美樹,横田麻衣,小川祥二郎,東 達也
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] DAPPZアイソトポログ誘導体化による胆汁酸のハイスループットLC/ESI-MS/MS定量法の開発2018

    • Author(s)
      城 彰宏,大谷沙織,小川祥二郎,東 達也
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] DAPTAD誘導体化-LC/ESI-MS/MSを用いる尿中グルクロン酸抱合型ビタミンD3代謝物の同定2018

    • Author(s)
      日本薬学会第138年会
    • Organizer
      吉村友佑,日比隆一郎,中田彬穂,小川祥二郎,東 達也
    • Related Report
      2017 Research-status Report
  • [Presentation] 誘導体化試薬アイソトポログを利用する低分子化合物のLC/ESI-MS/MS定量2017

    • Author(s)
      東 達也
    • Organizer
      第24回クロマトグラフィーシンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Girard P試薬アイソトポログを用いるsAVS試料中アルドステロンのLC/ESI-MS/MS定量2017

    • Author(s)
      赤石美帆,横田麻衣,杉浦悠毅,西本紘嗣郎,小川祥二郎,東 達也
    • Organizer
      第24回クロマトグラフィーシンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 誘導体化LC/ESI-MS/MSを用いるコレステロール代謝物の網羅的分析法の検討2017

    • Author(s)
      前川正充,河俣圭太,三枝大輔,小川祥二郎,東 達也,山口浩明,眞野成康
    • Organizer
      第28回日本臨床化学会東北支部総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 光学活性カルボン酸のLC/ESI-MS/MS用新規荷電誘導体化試薬の開発2017

    • Author(s)
      松本孝彬,山崎 航,戸田量子,小川祥二郎,東 達也
    • Organizer
      第30回バイオメディカル分析科学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] DAPTAD誘導体化-LC/ESI-MS/MSによる尿中グルクロン酸抱合型ビタミンD3代謝物の分析2017

    • Author(s)
      小川祥二郎,中田彬穂,日比隆一郎,吉村友佑,橘高宏貴,東 達也
    • Organizer
      第30回バイオメディカル分析科学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] 誘導体化-LC/ESI-MS/MSによる尿中グルクロン酸抱合型ビタミンD3代謝物の同定及び定量2017

    • Author(s)
      小川祥二郎,中田彬穂,日比隆一郎,吉村友佑,橘高宏貴,東 達也
    • 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] MALDI/TOF-MS(/MS)による血漿中DHEAS及びコルチゾール定量の試み2017

    • Author(s)
      中村将大,湯田啓太,小川祥二郎,杉浦悠毅,新間秀一,東 達也
    • 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] 誘導体化LC/ESI-MS/MSによるコレステロール代謝物の網羅的分析法に関する基礎的検討2017

    • Author(s)
      前川正充,河俣圭太,三枝大輔,小川祥二郎,東 達也,山口浩明,眞野成康
    • Organizer
      第28回クロマトグラフィー科学会議
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] METHOD FOR DERIVATIZING AN S-CIS-DIENE COMPOUND, DERIVATIZATION REAGENT KIT, AND METHOD FOR ANALYZING AN S-CIS-DIENE COMPOUND2017

    • Inventor(s)
      Higashi Tatsuya他4名
    • Industrial Property Rights Holder
      Higashi Tatsuya他4名
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Acquisition Date
      2019
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Method for derivatizing an s-cis-diene compound, derivatization reagent kit, and method for analyzing an s-cis-diene compound2017

    • Inventor(s)
      Higashi Tatusya,Ogawa Shoujiro
    • Industrial Property Rights Holder
      Higashi Tatusya,Ogawa Shoujiro
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report
    • Overseas

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Published: 2017-04-28   Modified: 2021-02-19  

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