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Study of impurity effects in organic crystal appearing in low frequency vibrational spectra and its application

Research Project

Project/Area Number 16H03882
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Optical engineering, Photon science
Research InstitutionShizuoka University

Principal Investigator

Sasaki Tetsuo  静岡大学, 電子工学研究所, 教授 (20321630)

Co-Investigator(Kenkyū-buntansha) 坂本 知昭  国立医薬品食品衛生研究所, 薬品部, 室長 (40311386)
大塚 誠  武蔵野大学, 薬学部, 教授 (90160548)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords微量不純物検出 / テラヘルツ分光 / 格子欠陥 / テラヘルツ / 医薬品 / 不純物検出 / テラヘルツ/赤外材料・素子 / 分析化学 / 薬学 / 応用光学・量子光工学 / 医薬品検査 / テラヘルツレーザー分光 / 中分子医薬品 / 分析科学 / 微量検出 / 中分子量
Outline of Final Research Achievements

We have shown that impurities as low as several tens of ppm in drug substance can be detected by accurate peak absorption frequency shift measurement using a high frequency precision terahertz spectroscopy system developed originally by us. Although a large part of impurity molecules contained in actual pharmaceutical production have similar species or molecular weight with drug substance, they are difficult to distinguish and detect for conventional chromatography methods. The new method developed in this study is useful because it can be detected regardless of the molecular species. Also, we have found that Middle Molecular Weight (MMW) pharmaceuticals that are attracting attention because of their low side effects show sharp spectra, and thus are suitable targets for applying this method. The data obtained in this work were released as a Terahertz spectral database for pharmaceuticals.

Academic Significance and Societal Importance of the Research Achievements

テラヘルツ周波数帯の分子振動が結晶構造に敏感であるという特徴を利用して「不純物分子そのものを検出するのではなく、その分子が周りの母体結晶に与える影響として捉える」という発想の転換で新規的測定手法を創出した。医薬品中の不純物は薬害を引き起こす可能性がある切実な課題であり、例えばサリドマイド事件では同じ分子式で表される光学異性体の微量混入が原因とされたが、本研究で開発した手法では光学異性体不純物の微量検出にも成功しており、実用性の高さを示した。学術的には結晶欠陥構造解析の為の分光学的アプローチを可能とした。本研究成果で構築したスペクトルデータベースは世界各国の大学や企業からアクセスされている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (34 results)

All 2019 2018 2017 2016 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (26 results) (of which Int'l Joint Research: 15 results,  Invited: 8 results) Remarks (3 results)

  • [Journal Article] 連続波テラヘルツレーザー分光測定による医薬品検査2019

    • Author(s)
      佐々木哲朗、坂本知昭
    • Journal Title

      PHARM TECH JAPAN

      Volume: 35 Pages: 125-130

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Sharp Absorption Peaks in THz Spectra Valuable for Crystal Quality Evaluation of Middle Molecular Weight Pharmaceuticals2018

    • Author(s)
      Sasaki Tetsuo、Sakamoto Tomoaki、Otsuka Makoto
    • Journal Title

      J Infrared Milli Terahz Waves

      Volume: 39 Issue: 9 Pages: 828-839

    • DOI

      10.1007/s10762-018-0494-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of Impurities in Organic Crystals by High-Accuracy Terahertz Absorption Spectroscopy2018

    • Author(s)
      Sasaki Tetsuo、Sakamoto Tomoaki、Otsuka Makoto
    • Journal Title

      Analytical Chemistry

      Volume: 90 Issue: 3 Pages: 1677-1682

    • DOI

      10.1021/acs.analchem.7b03220

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 医薬品結晶性評価のためのテラヘルツ分光スペクトル測定システムの開発2017

    • Author(s)
      佐々木哲朗
    • Journal Title

      分離技術

      Volume: 47 Pages: 234-239

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequency Resolution and Accuracy Improvement of a GaP CW THz Spectrometer2016

    • Author(s)
      Tetsuo Sasaki, Tadao Tanabe, and Jun-ichi Nishizawa
    • Journal Title

      Advances in Intelligent Systems and Computing Vol.519

      Volume: 519 Pages: 33-38

    • DOI

      10.1007/978-3-319-46490-9_5

    • ISBN
      9783319464893, 9783319464909
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Quantitative impurity measurement in pharmaceuticals by THz laser spectrometer2019

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Makoto Otsuka
    • Organizer
      PITTCON 2019 Philadelphia, USA, 2019.3.17-21
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 医薬品のテラヘルツ分光スペクトルデータベースの構築2019

    • Author(s)
      佐々木 哲朗、坂本 知昭、大塚 誠
    • Organizer
      日本薬学会 139年会(2019.3.20-23)千葉
    • Related Report
      2018 Annual Research Report
  • [Presentation] 連続波テラヘルツレーザー分光測定による医薬品品質検査2019

    • Author(s)
      佐々木 哲朗、坂本 知昭、大塚 誠、西澤 潤一
    • Organizer
      学振182委員会研究会, 2019.2.12, えんてつ駅前貸会議室、浜松
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] High accuracy and high resolution terahertz spectroscopy for impurity detection in pharmaceutical drugs2018

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Makoto Otsuka
    • Organizer
      the 4th International Conference on Nano Electronics Research Education 2018 (ICNERE 2018), 2018.11.28
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A trial application of terahertz spectroscopy as a pharmaceutical process monitoring tool2018

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto
    • Organizer
      The 3rd International Symposium on Biomedical Engineering (ISBE2018), 2018.11.9.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Quantitative Impurity Measurement In Organic Crystals By Precise Measurements Of THz Absorption Frequencies2018

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Makoto Otsuka
    • Organizer
      43rd International Conference on Infrared, Millimeter and Terahertz Waves (IRMMW-THz 2018), Nagoya, Japan, 2018.9.10 - 9.14
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of a-Cyclodextrin Hexahydrate Crystal by High Accuracy Terahertz Spectroscopy2018

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Makoto Otsuka
    • Organizer
      ICS2018, 2018.4.29, Sophia Univ., Tokyo
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 連続波テラヘルツ分光スペクトルを利用した医薬品分析2018

    • Author(s)
      佐々木哲朗
    • Organizer
      第24回 マイクロシステム融合研究会, 東北大学, 仙台, 2018.6.15
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Spectroscopy by coherent monochromatic terahertz wave2018

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Makoto Otsuka
    • Organizer
      FY 2017 RIEC Annual Meeting on Cooperative Research Projects "Compass for Next Generation ICT", RIEC, Tohoku Univ., Miyagi
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 高精度テラヘルツ分光スペクトル測定による有機結晶中の高感度不純物検出2018

    • Author(s)
      佐々木 哲朗, 坂本 知昭, 大塚 誠
    • Organizer
      日本薬学会 138年会 金沢
    • Related Report
      2017 Annual Research Report
  • [Presentation] 高精度テラヘルツ分光スペクトル測定による中分子量医薬品のスペクトル観察2017

    • Author(s)
      佐々木 哲朗, 坂本 知昭, 大塚 誠
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター、宮城県仙台市
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Continuous wave terahertz laser spectrometer and its applications for pharmaceuticals2017

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Tadao Tanabe, and Jun-ichi Nishizawa
    • Organizer
      PITTCON 2017
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2017-03-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Detection of impurities contained in organic crystals by terahertz spectroscopy measurement2017

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Makoto Otsuka
    • Organizer
      The 2nd International Symposium on Biomedical Engineering, Tokyo Institute of Technology, Tokyo
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Continuous Wave Gallium Phosphide THz Spectrometer applied for Pharmaceutical Industry2017

    • Author(s)
      Tetsuo Sasaki, Tomoaki Sakamoto, Makoto Otsuka
    • Organizer
      8th International THz-Bio Workshop, (THz-BIO2017), Frascati, Italy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of CW THz signal generator using GaP crystal and its application for spectroscopy2017

    • Author(s)
      Tetsuo Sasaki
    • Organizer
      Department of Microelectronic Systems, Faculty of Electronics, Telecommunications and Informatics, Gdansk University of Technology Seminar talk
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Fluorine resin-coating of hydrated molecules for stable terahertz spectroscopy at low temperature2017

    • Author(s)
      Tetsuo Sasaki
    • Organizer
      42nd International Conference on Infrared, Millimeter and Terahertz Waves (IRMMW-THz 2017), Cancun, Mexico
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] テラヘルツ波を用いた光医工学研究- 分光スペクトル測定による医薬品結晶性評価2017

    • Author(s)
      佐々木哲朗
    • Organizer
      静岡大学 超領域研究推進本部 第11回超領域研究会、静岡大学浜松キャンパス、静岡
    • Related Report
      2017 Annual Research Report
  • [Presentation] テラヘルツ分光スペクトル測定による有機結晶含有微量不純物検出2017

    • Author(s)
      佐々木哲朗、坂本知昭、大塚誠
    • Organizer
      第46回結晶成長国内会議(JCCG-46)、ホテルコンコルド浜松、静岡
    • Related Report
      2017 Annual Research Report
  • [Presentation] 高周波数精度連続波テラヘルツ分光吸収スペクトル測定による有機結晶中の微量不純物の高感度検出2017

    • Author(s)
      佐々木哲朗、坂本知昭、大塚誠
    • Organizer
      第78回応用物理学会秋季学術講演会、福岡国際会議場(福岡)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 連続波テラヘルツ分光スペクトル測定装置とその応用-医薬品評価に向けて-2017

    • Author(s)
      佐々木哲朗
    • Organizer
      FIR CENTER セミナー、福井大学 遠赤外領域開発研究センター
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 医薬品結晶性評価のためのテラヘルツ分光スペクトル測定システムの開発2017

    • Author(s)
      佐々木哲朗
    • Organizer
      分離技術会 第12回東海地区分離技術講演会
    • Place of Presentation
      静岡大学浜松キャンパス、静岡県浜松市
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Development of GaP continuous wave terahertz spectrometer - terahertz spectroscopy and imaging for and pharmaceutical applications2016

    • Author(s)
      Tetsuo Sasaki
    • Organizer
      The 1st International Symposium on Biomedical Engineering
    • Place of Presentation
      Tokyo Medical and Dental University, Tokyo
    • Year and Date
      2016-11-10
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Frequency Resolution and Accuracy Improvement of a GaP CW THz Spectrometer2016

    • Author(s)
      Tetsuo Sasaki, Tadao Tanabe, Jun-ichi Nishizawa
    • Organizer
      The 15th International Conference on Global Research and Education (Inter-Academia 2016)
    • Place of Presentation
      Warsaw, Poland
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] requency Accuracy and Resolution of a GaP Continuous-Wave Terahertz Spectrometer2016

    • Author(s)
      Tetsuo Sasaki, Tadao Tanabe, Jun-ichi Nishizawa
    • Organizer
      41st International Conference on Infrared, Millimeter and Terahertz Waves (IRMMW-THz 2016)
    • Place of Presentation
      Copenhagen, Denmark
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CW THz Signal Generator based on DFG in GaP and its Applications for Spectroscopy2016

    • Author(s)
      Tetsuo Sasaki, Tadao Tanabe, Tomoaki Sakamoto, Jun-ichi Nishizawa
    • Organizer
      BIT's 5th Annual World Congress of Advanced Materials-2016 (WCAM-2016)
    • Place of Presentation
      Chongqing, China
    • Year and Date
      2016-06-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 連続波テラヘルツ光源とその応用 - 医薬品の分光分析 -2016

    • Author(s)
      佐々木哲朗
    • Organizer
      光とレーザーの科学技術フェア2016 特別交流シンポジウム
    • Place of Presentation
      科学技術館、東京都千代田区
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Remarks] THz spectral database for Pharmaceuticals

    • URL

      https://www.rie.shizuoka.ac.jp/~thz/database/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 佐々木研究室の研究内容 「微量不純物検出・定量」

    • URL

      https://www.rie.shizuoka.ac.jp/~thz/HR-THz.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 佐々木研究室HP

    • URL

      http://www.rie.shizuoka.ac.jp/~thz/index.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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