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Analysis of new-generation neurosteroids in brain by LC/MS/MS coupled to derivatization with ESI-enhancing and deuterium-labeling reagents

Research Project

Project/Area Number 26460043
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)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords神経活性ステロイド / ESI増強重水素標識試薬 / LC/MS/MS / 精神・神経疾患 / アンドロゲン / ビタミンD代謝物 / 胆汁酸 / 創薬 / 分析科学 / 誘導体化試薬 / ESI増強 / 重水素標識 / 向精神薬 / アロプレグナノロン
Outline of Final Research Achievements

Qualitative and quantitative analyses of new-generation neurosteroids (NSs), such as androgens and bile acids, can contribute to the discovery and development of new antipsychotic agents and therapy for psychiatric disorders targeting neurosteroidogenesis. In this study, novel LC/MS/MS assays coupled to derivatization with the ESI-enhancing and deuterium-labeling reagents were developed. Using the developed method, we demonstrated the possibility that mianserin and mirtazapine elevate the brain allopregnanolone concentration and have anxiolytic effects. Three unconjugated bile acids (BAs), including chenodeoxycholic acid, were identified and quantified as the major BAs in the rat brain. Based on the comparison with their serum levels, we found that most BAs in the brain are derived from the periphery and the major mechanism for the transportation of the unconjugated BAs to the brain is the passive diffusion.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 2014

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 8 results) Presentation (16 results) (of which Invited: 2 results)

  • [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
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Application of Cookson-type reagents for biomedical HPLC and LC/MS analyses: a brief overview2017

    • Author(s)
      T. Higashi, K. Shimada
    • Journal Title

      Biomedical Chromatography

      Volume: 31 Issue: 1

    • DOI

      10.1002/bmc.3808

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative evaluation of new Cookson-type reagents for LC/ESI-MS/MS assay of 25-hydroxyvitamin D3 in neonatal blood samples2016

    • Author(s)
      S. Ogawa, H. Kittaka, K. Shinoda, S. Ooki, A. Nakata, T. Higashi
    • Journal Title

      Biomedical Chromatography

      Volume: 30 Issue: 6 Pages: 938-945

    • DOI

      10.1002/bmc.3633

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Method for Simultaneous Determination of 25-Hydroxyvitamin D<sub>3</sub> and Its 3-Sulfate in Newborn Plasma by LC/ESI-MS/MS after Derivatization with a Proton-Affinitive Cookson-Type Reagent2016

    • Author(s)
      T. Higashi, M. Yokota, A. Goto, S. Ogawa, K. Komatsu, T. Sugiura, M. Satoh, F. Nomura
    • Journal Title

      Mass Spectrometry

      Volume: 5 Issue: 2 Pages: S0051-S0051

    • DOI

      10.5702/massspectrometry.S0051

    • NAID

      130005263499

    • ISSN
      2186-5116, 2187-137X
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Development and validation of the simultaneous measurement of four vitamin D metabolites in serum by LC-MS/MS for clinical laboratory applications2016

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

      Anal Bioanal Chem

      Volume: 408 Issue: 27 Pages: 7617-7627

    • DOI

      10.1007/s00216-016-9821-4

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Chemical derivatization for enhancing sensitivity during LC/ESI-MS/MS quantification of steroids in biological samples: a review2016

    • Author(s)
      T. Higashi, S. Ogawa
    • Journal Title

      Journal of Steroid Biochemistry and Molecular Biology

      Volume: 162 Pages: 57-69

    • DOI

      10.1016/j.jsbmb.2015.10.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Isotope-coded ESI-enhancing derivatization reagents for differential analysis, quantification and profiling of metabolites in biological samples by LC/MS: a review2016

    • Author(s)
      T. Higashi, S. Ogawa
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 130 Pages: 181-193

    • DOI

      10.1016/j.jpba.2016.04.033

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Methods for differential and quantitative analyses of brain neurosteroid levels by LC/MS/MS with ESI-enhancing and isotope-coded derivatization2016

    • Author(s)
      T. Higashi, N. Aiba, T. Tanaka, K. Yoshizawa, S. Ogawa
    • Journal Title

      Journal of Pharmaceutical and Biomedical Analysis

      Volume: 117 Pages: 155-162

    • DOI

      10.1016/j.jpba.2015.08.040

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Methods for determination of fingernail steroids by LC/MS/MS and differences in their contents between right and left hands2016

    • Author(s)
      T. Higashi, K. Yamagata, Y. Kato, Y. Ogawa, K. Takano, Y. Nakaaze, T. Iriyama, J. Z. Min, S. Ogawa
    • Journal Title

      Steroids

      Volume: 109 Pages: 60-65

    • DOI

      10.1016/j.steroids.2016.02.013

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Analysis of urinary vitamin D3 metabolites by liquid chromatography/tandem mass spectrometry with ESI-enhancing and stable isotope-coded derivatization2014

    • Author(s)
      S. Ogawa, S. Ooki, K. Shinoda, T. Higashi
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 406 Issue: 26 Pages: 6647-6654

    • DOI

      10.1007/s00216-014-8095-y

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] ICD-LC/ESI-MS/MSによる尿中テトラヒドロコルチコステロイドグルクロニドの定量法の開発2017

    • Author(s)
      松本孝彬,山崎 航,小川祥二郎,三田村邦子,池川繁男,東 達也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 種々のCookson型試薬による7-dehydrocholesterol誘導体のプロトン親和力とESI-MS感度との関係2017

    • Author(s)
      小川祥二郎,渡部ひとみ,茶谷 仁,島田洋輔,坪郷 哲,後藤 了,東 達也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research 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系の構築2017

    • Author(s)
      河俣圭太,前川正充,三枝大輔,小川祥二郎,東 達也,山口浩明,眞野成康
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cookson型誘導体化試薬のESI-MS/MS分析における感度向上能と量子計算に基づくプロトン親和力との関係2016

    • Author(s)
      小川祥二郎,渡部ひとみ,茶谷 仁,島田洋輔,恒岡弥生,後藤 了,東 達也
    • Organizer
      日本分析化学会第65年会
    • Place of Presentation
      北海道大学工学部(北海道)
    • Year and Date
      2016-09-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] LC/ESI-MS/MSを用いた新生児血漿中25-hydroxyvitamin D3及びその硫酸抱合体の同時定量2016

    • Author(s)
      横田麻衣,後藤彩佳,小川祥二郎,小松賢司,杉浦崇浩,東 達也
    • Organizer
      日本分析化学会第65年会
    • Place of Presentation
      北海道大学工学部(北海道)
    • Year and Date
      2016-09-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] DAPTADアイソトポログを用いた血漿中25-hydroxyvitamin D3の高感度・ハイスループットLC/ESI-MS/MS分析法の開発2016

    • Author(s)
      橘高宏貴,中田彬穂,小川祥二郎,東 達也
    • Organizer
      第29回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      京都大学桂キャンパス(京都府)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 非侵襲ステロイド検査試料としての爪の有用性2016

    • Author(s)
      小川祥二郎,高野 香,中畔勇太郎,閔 俊哲,東 達也
    • Organizer
      第29回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      京都大学桂キャンパス(京都府)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 誘導体化-LC/ESI-MS/MSによる新生児ビタミンD欠乏症の精密診断法の開発2016

    • Author(s)
      東 達也
    • Organizer
      第64回質量分析総合討論会
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪府)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ESI増強誘導体化試薬を用いるラット脳内胆汁酸のLC/MS/MS定量2016

    • Author(s)
      小川祥二郎, 都丸晃輝, 渡辺趣衣, 眞野成康,東 達也
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] カルボン酸用ESI活性誘導体化試薬の開発と生体試料分析への応用2015

    • Author(s)
      都丸晃輝, 小川祥二郎, 渡辺趣衣, 眞野成康,東 達也
    • Organizer
      第26回クロマトグラフィー科学会議
    • Place of Presentation
      九州大学医系キャンパス コラボステーション(福岡県)
    • Year and Date
      2015-11-11
    • Related Report
      2015 Research-status Report
  • [Presentation] ESI増強重水素試薬を用いる脳内神経活性ステロイドのレベル変動解析2015

    • Author(s)
      相葉尚人, 田中智哉, 大和 遼, 吉澤一巳, 小川祥二郎, 東 達也
    • Organizer
      第26回クロマトグラフィー科学会議
    • Place of Presentation
      九州大学医系キャンパス コラボステーション(福岡県)
    • Year and Date
      2015-11-11
    • Related Report
      2015 Research-status Report
  • [Presentation] ステロイド検査試料としての爪の評価:左右の手の爪中ステロイドの含量差2015

    • Author(s)
      小川祥二郎,加藤由那,高野 香,中畔勇太郎,山形憲一郎,閔 俊哲,東 達也
    • Organizer
      第40回日本医用マススペクトル学会年会
    • Place of Presentation
      アクトシティ浜松(静岡県)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
  • [Presentation] ESI活性重水素標識試薬を用いるラット脳内神経活性ステロイド分析法の開発2015

    • Author(s)
      相葉尚人,田中智哉,小川祥二郎,東 達也
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸サンボーホール(兵庫県)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] カルボン酸用新規ESI増強重水素標識試薬の合成とLCにおける同位体効果の評価2015

    • Author(s)
      小川祥二郎,高藤季里子,堀江裕紀子,池川繁男,東 達也
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸サンボーホール(兵庫県)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ESI増強重水素標識試薬を用いた尿中ビタミンD3代謝物のLC/MS/MS分析法の開発2014

    • Author(s)
      大木 智,篠田健太,小川祥二郎,東 達也
    • Organizer
      第39回日本医用マススペクトル学会年会
    • Place of Presentation
      三井ガーデンホテル千葉(千葉県)
    • Year and Date
      2014-10-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 低分子化合物のLC/ESI-MS/MS用誘導体化:検出感度の向上と構造微小差の弁別2014

    • Author(s)
      東 達也
    • Organizer
      第39回日本医用マススペクトル学会年会
    • Place of Presentation
      三井ガーデンホテル千葉(千葉県)
    • Year and Date
      2014-10-16
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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