Determination of urinary metabolites of XLR-11 by liquid chromatography–quadrupole time-of-flight mass spectrometry

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• 作者：Moonhee Jang ; In Sook Kim ; Yu Na Park ; Jihyun Kim…
• 关键词：Synthetic cannabinoid ; XLR ; 11 ; UR ; 144 ; Urinary metabolites ; Liquid chromatography–quadrupole time ; of ; flight mass spectrometry
• 刊名：Analytical and Bioanalytical Chemistry
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：408
• 期：2
• 页码：503-516
• 全文大小：2,003 KB
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• 作者单位：Moonhee Jang (1)
  In Sook Kim (2)
  Yu Na Park (2)
  Jihyun Kim (1)
  Inhoi Han (1)
  Seungkyung Baeck (1)
  Wonkyung Yang (1)
  Hye Hyun Yoo (2)
  
  1. National Forensic Service, 139 Jiyang-ro, Yangcheon-gu, Seoul, 158-707, Republic of Korea
  2. Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 426-791, Republic of Korea
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Analytical Chemistry
  Food Science
  Inorganic Chemistry
  Physical Chemistry
  Monitoring, Environmental Analysis and Environmental Ecotoxicology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1618-2650

文摘

Recently, use of novel synthetic cannabinoids has increased greatly despite worldwide efforts to regulate these drugs. XLR-11 ((1-[5'-fluoropentyl]indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone), a fluorinated synthetic cannabinoid with a tetramethylcyclopropyl moiety, has been frequently abused since 2012. XLR-11 produces a number of metabolites in common with its non-fluorinated parent analogue, UR-144 ((1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone). Therefore, it is essential to develop effective urinary markers to distinguish between these drugs. In this study, we investigated the metabolic profile of authentic human urine specimens from suspected users of XLR-11 using liquid chromatography–quadrupole time-of-flight mass spectrometry. Furthermore, we quantified four potential XLR-11 metabolites by using commercially available reference standards. In vitro metabolism of XLR-11 and UR-144 using human liver microsomes was also investigated to compare patterns of production of hydroxypentyl metabolites. Urine samples were prepared with and without enzymatic hydrolysis, and subjected to solid-phase extraction. We identified 19 metabolites generated by oxidative defluorination, hydroxylation, carboxylation, dehydrogenation, glucuronidation, and combinations of these reactions. Among the identified metabolites, 12 were generated from a cyclopropyl ring-opened XLR-11 degradation product formed during smoking. The XLR-11 metabolite with a hydroxylated 2,4-dimethylpent-1-ene moiety was detected in most specimens after hydrolysis and could be utilized as a specific marker for XLR-11 intake. Quantitative results showed that the concentration ratio of 5- and 4-hydroxypentyl metabolites should also be considered as a useful marker for differentiating between the abuse of XLR-11 and UR-144. Keywords Synthetic cannabinoid XLR-11 UR-144 Urinary metabolites Liquid chromatography–quadrupole time-of-flight mass spectrometry