Liquid chromatography–mass spectrometry studies on the isomeric 1-fluorobenzyl-3-naphthoyl-indoles: FUB-JWH-018 and five isomers

Abstract

Purpose

One of the ongoing research subjects for forensic analysts is differentiating halogen positional isomers of newly-emerging synthetic cannabinoids. The purpose of this study is to elucidate liquid chromatographic and mass spectrometric conditions applicable to the differentiation of such derivatives.

Methods

High-performance liquid chromatography (HPLC) coupled with triple quadrupole mass spectrometry (QqQ-MS) and linear ion trap time-of-flight mass spectrometry (IT-TOF-MS) using electrospray ionization (ESI) in its positive ion mode were utilized to analyze six model compounds, FUB-JWH-018 and five positional isomers having structures of 1- or 2-naphthoyl-substituted 1H-indole-3-carboxylates with N-substituted positional isomeric fluorobenzyl groups (2-fluorobenzyl, 3-fluorobenzyl, and 4-fluorobenzyl).

Results

The chromatographic separation of the six isomers was successfully achieved by HPLC using a pentafluorophenylpropyl-bonded reversed-phase adsorbent. The positive ESI-QqQ-MS could discriminate fluorobenzyl isomers having a same naphthoyl structure via the relative abundance of the two product ions in the collision-induced dissociation reaction. ESI-IT-TOF-MS in its positive ion mode successfully distinguished three ring positional isomers in both naphthoyl scaffolds on the basis of the differences in the abundance of oxomethylium ion attributed to C16H11FNO+ (m/z 252).

Conclusions

The use of ESI-QqQ-MS and ESI-IT-TOF-MS in its positive ion mode coupled with LC using a pentafluorophenylpropyl-bonded silica column is applicable to MS-aided differentiation and the chromatographic separation of FUB-JWH-018 positional isomers.

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Acknowledgements

This work was funded by the domestically programmed Grant for the regional society from the Gifu Prefectural Research Institute for Health and Environmental Sciences. The study was supported by the Health and Labour Sciences Research Grants 2015 and 2016 to K. Kitaichi (Research on Regulatory Science of Pharmaceuticals and Medical Devices, No. 27170401). A portion of this work was supported by the governmental program on a survey of designer drugs in the illegal drug market, supervised by Gifu Prefectural Government, Japan. The study was also supported by the Grants for research on regional health, medical, and welfare to T. Ito (The Daido Life Welfare Foundation). We are thankful to Shizuoka Prefectural Government, Japan, for providing the two illegal herbal products for inspection. We acknowledge the Gifu Regional Consortium on the Development of Analytical Procedures for Legal Highs operated by Gifu Pharmaceutical University and the Gifu Prefectural Research Institute for Health and Environmental Sciences for overseeing the experimental protocols.

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Correspondence to Erina Kohyama or Tetsuro Ito.

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Chikumoto, T., Furukawa, R., Kohyama, E. et al. Liquid chromatography–mass spectrometry studies on the isomeric 1-fluorobenzyl-3-naphthoyl-indoles: FUB-JWH-018 and five isomers. Forensic Toxicol 37, 113–120 (2019). https://doi.org/10.1007/s11419-018-0442-9

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Keywords

  • Synthetic cannabinoids
  • LC–ESI-IT-TOF-MS
  • Regioisomer differentiation
  • Fluorobenzyl indoles
  • Pentafluorophenylpropyl stationary phase