Development of sensitive analytical method for metabolites of abused drugs in human samples

• Project/Area Number: 17K15880
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Hasegawa Koutaro 浜松医科大学, 医学部, 准教授 (40574025)
• Research Collaborator: AMIN wurita
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 危険ドラッグ / 合成カンナビノイド / 尿中代謝物 / 死後体内分布/再分布 / LC-MS/MS / GC-MS / 法医中毒学 / 人体代謝物 / 質量分析

Outline of Final Research Achievements

Sensitive analytical methods for various abused drugs and its metabolites in authentic human samples including urines using liquid-chromatography tandem-mass-spectrometry and/or gas-chromatography mass-spectrometry were newly established in this study. Authentic human samples such as body fluids and solid tissues for analysis were obtained from autopsies. In intoxication cases due to intake of synthetic cannabinoids, their specific metabolites excreted in urine are thought to be useful as biomarker, because it is very difficult to detect their unchanged parent molecular in urine samples owing to their distribution, excretion and manner of metabolism in human body; concentrations of unchanged synthetic cannabinoids in urine are typically some magnitudes lower than that of metabolites. In this study, metabolites of synthetic cannabinoids and abused drugs were successfully determined in human urine samples, and their usefulness as biomarker were also demonstrated.

Academic Significance and Societal Importance of the Research Achievements

合成カンナビノイドと側鎖の長いカチノン類では，乱用者の尿からは未変化体を検出する事が大変困難である．ヒト尿は最も侵襲性が少なく、救急外来等での採取も容易であり極めて有用な試料である．この研究では、各種危険ドラッグ類・乱用薬物の尿中代謝産物に焦点を当て，検出・定量法の開発を目指す．実際の乱用者の尿中危険ドラッグ代謝産物研究論文は極めて少ない．この研究では，実際の薬毒物乱用事例での試料を用いて研究を行うことにより，エビデンスレベル・参照価値の高い成果報告が期待される．

Research Products

• [Int'l Joint Research] Inner Mongolia Medical University(中国)
• [Journal Article] Fatal zolpidem poisoning due to its intravenous self-injection: Post mortem distribution/redistribution of zolpidem and its predominant metabolite zolpidem phenyl-4-carboxylic acid in body fluids and solid tissues in an autopsy case (2018)
  • Author(s): Koutaro Hasegawa, Amin Wurita, Hideki Nozawa, Itaru Yamagishi, Kayoko Minakata, Kanako Watanabe, Osamu Suzuki
  • Journal Title: Forensic Science International Volume: 290 Pages: 111-120
  • DOI: 10.1016/j.forsciint.2018.06.044
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification and quantification of predominant metabolites of synthetic cannabinoid MAB-CHMINACA in an authentic human urine specimen. (2018)
  • Author(s): 2.Hasegawa K, Minakata K, Gonmiri K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O
  • Journal Title: Drug Testing and Analysis Volume: 10 Issue: 2 Pages: 365-371
  • DOI: 10.1002/dta.2220
  • Peer Reviewed
• [Presentation] Identification and quantification of synthetic cannabinoid 5F-ADB-PINACA and its predominant metabolites in an authentic human urine specimen (2018)
  • Author(s): Koutaro Hasegawa, Amin Wurita, Kayoko Minakata, Hideki Nozawa, Itaru Yamagishi, Kanako Watanabe, Osamu Suzuki
  • Organizer: TIAFT(The International Association of Forensic Toxicologists) 2018
  • Int'l Joint Research
• [Presentation] ヒト尿中からの合成カンナビノイド５F-ADB-PINACA代謝物の検出 (2017)
  • Author(s): 長谷川弘太郎
  • Organizer: 第39回日本法医学会学術中部地方集会
• [Presentation] ヒト尿中からの合成カンナビノイドMAB-CHMINACAの代謝物の同定と定量 (2017)
  • Author(s): 長谷川弘太郎
  • Organizer: 日本法中毒学会第36年会