Development of the prominent labeling reagent for LC/MS/MS and its application to the analysis of the biomolecules

• Project/Area Number: 19590036
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: SANTA Tomofumi The University of Tokyo, 大学院・薬学系研究科, 准教授 (30187306)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 分析化学 / 標識試薬 / クロマトグラフィー / 質量分析 / LC / MS / 生体分子 / 新生児マススクリーニング

Research Abstract

近年、高速液体クロマトグラフィー(LC)とタンデム型質量分析器(MS/MS)を組み合わせたLC/MS/MS法が広く用いられている。本研究では、LC/MS/MS法における検出感度および選択性の向上を目的とした標識試薬を合成した。また、合成した標識試薬を用いて疾患のマーカーとなる生体分子の高感度な分析法を開発した。本研究で開発した分析法は、新生児のマススクリーニング法として海外で用いられている。

Research Products

• [Journal Article] Synthesis of 4-[2-(N, N-dimethylamino) ethylamino sulfonyl]-7-N-methylhydrazino-2, 1, 3-ben zoxadiazole (DAABD-MHz) as a derivatization reagent for aldehydes in liquid chromatography/electrospray ionization-tandem mass spectrometry (2008)
  • Author(s): Santa T, Al-Dirbashi OY, Ichibangase T, Rashed MS, Fukushima T, Imai K.
  • Journal Title: Biomed. Chromatogr. 22 Pages: 115-118
  • Peer Reviewed
• [Journal Article] Al-Makhadab M Rapid UPLC-MS/MS method for routine analysis of plasma pristanic, phytanic and very-long chain fatty acid markers of peroxisomal disorders (2008)
  • Author(s): Al-Dirbashi OY, Santa T, Rashed MS, Al-Hassnan Z, Shimozawa N, Chedrawi AK, Jacob M
  • Journal Title: J. Lipid Res. 49 Pages: 1855-1862
  • Peer Reviewed
• [Journal Article] Rcent progress in the development of derivatization reagents having a benzofurazan structure (2008)
  • Author(s): Santa T, Fukushima T, Ichibangase T, Imai K.
  • Journal Title: Biomed. Chromatogr. 22 Pages: 343-353
  • Peer Reviewed
• [Journal Article] Synthesis of 4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-N-methylhydrazino-2,1,3-benzoxadiazole(DAABD-MHz)as a derivatization reagent for aldehydes in LC/MS/MS (2008)
  • Author(s): Santa, Tomofumi
  • Journal Title: Biomedical Chromatography 22 Pages: 115-118
  • Peer Reviewed
• [Journal Article] Recent progress in the development of derivatization reagents having a benzofurazan structure (2008)
  • Author(s): Santa, Tomofumi
  • Journal Title: Biomedical Chromatography 22 Pages: 343-353
  • Peer Reviewed
• [Journal Article] Rapid UPLC-MS/MS method for routine analysis of plasma pristanic, phytanic and very-long chain fatty acid markers of peroxisomal disorders (2008)
  • Author(s): Al-Dirbashi, Osama Y
  • Journal Title: Journal of Lipid Research 49 Pages: 1855-1862
  • Peer Reviewed
• [Journal Article] Synthesis of benzofurazan derivatization reagents for carboxylic acids in liquid chromatography/ electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) (2007)
  • Author(s): Santa T, Al-Dirbashi OY, Ichibangase T, Fukushima T, Rashed MS, Funatsu T, Imai K.
  • Journal Title: Biomed. Chromatogr. 21 Pages: 1207-1213
  • Peer Reviewed
• [Journal Article] Derivatization reagents in liquid chromatography/electrospray ionization tandem mass spectrometry for biomedical analysis (2007)
  • Author(s): Santa T, Al-Dirbashi OY, Fukushima T.
  • Journal Title: Drug Disc. Ther. 1 Pages: 108-118
  • Peer Reviewed
• [Journal Article] Analysis of organic acid markers relevant to inherited metabolic diseases by ultra-performance liquid chromatography/tandem mass spectrometry as benzofurazan derivatives (2007)
  • Author(s): Al-Dirbashi OY, Santa T, Al-Qahtani K, Al-Amoudi M, Rashed MS.
  • Journal Title: Rapid Commun. Mass Spectrom. 21 Pages: 1984-1990
  • Peer Reviewed
• [Journal Article] Synthesis of benzofurazan derivatization reagents for carboxylic acids in liquid chromatography/electrospray ionization-tandem mass spectrometry (2007)
  • Author(s): Santa, Tomofumi
  • Journal Title: Biomedical Chromatography 21 Pages: 1207-1213
  • Peer Reviewed
• [Journal Article] Derivatization reagents in liquid chromatography/electrospray ionization tandem mass spectrometry for biomedical analysis (2007)
  • Author(s): Santa, Tomofumi
  • Journal Title: Drug Discovery and Therapeutics 1 Pages: 108-118
  • Peer Reviewed
• [Presentation] Development of benzofurazan derivatization reagents for LC-MS/MS and application to the analysis of bio-markers of peroxisomal disorders (2008)
  • Author(s): Al-Dirbashi OY, Santa T, Shimozawa N, Rashed MS.
  • Organizer: Japan-China Joint Medicine Workshop on Drug Discoveries and Therapeutics
  • Place of Presentation: Tokyo
• [Presentation] Synthesis of benzofurazan derivatization reagent and analysis of fatty acids by LC/FL and LC/MS (2008)
  • Author(s): Santa T, Osama Y Al-Dirbashi.
  • Organizer: ISLS 2008 (XIII International Synposium on Luminescence Spectrometry)
  • Place of Presentation: Bologna
• [Presentation] ベンゾフラザン骨格を有するLC/MS/MS用標識試薬の開発と疾患マーカーの高感度分析 (2008)
  • Author(s): 三田智文, Osama Y Al-Dirbashi
  • Organizer: 第15回クロマトグラフィーシンポジウム
  • Place of Presentation: 静岡
• [Presentation] ベンゾフラザン骨格を有するLC/MS/MS用標識試薬の開発と応用 (2008)
  • Author(s): 三田智文, Osama Y Al-Dirbashi
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
• [Presentation] Development of benzofurazan labeling reagents for LC/MS/MS and their application to biomarker analysis (2007)
  • Author(s): Santa, Tomofumi
  • Organizer: 6^<th> AFMC International Medicinal Chemistry Symposium
  • Place of Presentation: Istanbul
  • Year and Date: 2007-07-10
• [Presentation] Novel diagnostic methods for glutaric acidemia type 1 (2007)
  • Author(s): Al-Dirbashi OY, Rashed MS, Santa T, Al-Hassnan Z
  • Organizer: SSIEM2007 (Society for the Study of Inborn Errors of Metabolism)
  • Place of Presentation: Hamburg
• [Presentation] Development of benzofurazan labeling reagents for LC/MS/MS and their application to biomarker analysis. (2007)
  • Author(s): Santa T, Al-Dirbashi OY, Rashed MS
  • Organizer: 6^<th> AFMC International Medicinal Chemistry Symposium
  • Place of Presentation: Istanbul
• [Presentation] Development of benzofurazan labeling reagents for LC/MS/MS and their application to biomarker analysis (2007)
  • Author(s): Santa T, Al-Dirbashi OY, Rashed MS
  • Organizer: China-Japan Joint Medicine Workshop on Drug Discoveries and Therapeutics
  • Place of Presentation: Jinan