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Characterization of in vitro phase I metabolites of methamnetamine in human liver microsomes by liquid chromatography-quadrupole time-of-flight mass spectrometry

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Abstract

N-Methyl-1-(naphthalen-2-yl)propan-2-amine (methamnetamine, PAL-1046) is an amphetamine-based new psychoactive substance (NPS). Methamnetamine has been reported to cause excessive release of serotonin, and it is classified as an empathogen or entactogen. It is not regulated as a controlled substance in most countries, and there are no studies on its metabolism. In this study, in vitro phase I metabolism of methamnetamine in human liver microsomes (HLM) and flavin-containing monooxygenase (FMO) was investigated by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Eight metabolites of methamnetamine were identified and were structurally characterized achieved by a combination of accurate mass analysis and tandem mass spectrometry. The identified metabolic processes include N-demethylation, N-hydroxylation, aromatic hydroxylation, and a combination of these processes. N-Hydroxylated metabolites were confirmed based on expressed FMOs. The major metabolite was formed from methamnetamine via hydroxylation of the naphthalene ring after the in vitro phase I process. These results could help detect methamnetamine ingestion by NPS abusers.

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Funding

This study was supported by the Ministry of Food and Drug Safety of Korea (19181MFDS401).

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Authors and Affiliations

  1. Pharmacological Research Division, Toxicological and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, 187 Osong Saengmyeong 2-ro, Heungdeok-gu, Chungju-shi, 28159, Chungccheongbuk-do, Republic of Korea

    Young-ki Hong, Young-Hoon Kim, Jin-Moo Lee, Sun-Ok Choi & Mi Sun Kang

  2. Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, 15588, Republic of Korea

    Hye Hyun Yoo

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  1. Young-ki Hong
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Contributions

Data evaluation, formal analysis, writing—original draft: Young-Ki Hong.

Conceptualization, supervision: Young-Hoon Kim.

Formal analysis, methodology: Jin-Moo Lee.

Writing—review and editing, Validation: Hye Hyun Yoo.

Funding acquisition, project administration: Sun-Ok Choi.

Writing—review and editing: Mi Sun Kang.

Corresponding author

Correspondence to Mi Sun Kang.

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Hong, Yk., Kim, YH., Lee, JM. et al. Characterization of in vitro phase I metabolites of methamnetamine in human liver microsomes by liquid chromatography-quadrupole time-of-flight mass spectrometry. Int J Legal Med 135, 1471–1476 (2021). https://doi.org/10.1007/s00414-021-02594-z

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