In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s

Ju Hyun Kim; Hee Seung Kim; Tae Yeon Kong; Joo Young Lee; Jin Young Kim; Moon Kyo In; Hye Suk Lee

doi:10.1016/j.jpba.2015.11.023

In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s

Ju Hyun Kim, Hee Seung Kim, Tae Yeon Kong, Joo Young Lee, Jin Young Kim, Moon Kyo In, Hye Suk Lee

Pharmacy

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

In vitro metabolism of a new synthetic cannabinoid, EAM-2201, has been investigated with human liver microsomes and major cDNA-expressed cytochrome P450 (CYP) isozymes using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Incubation of EAM-2201 with human liver microsomes in the presence of NADPH resulted in the formation of 37 metabolites, including nine hydroxy-EAM-2201 (M1-M9), five dihydroxy-EAM-2201 (M10-M14), dihydrodiol-EAM-2201 (M15), oxidative defluorinated EAM-2201 (M16), two hydroxy-M16 (M17 and M18), three dihydroxy-M16 (M19-M21), N-dealkyl-EAM-2201 (M22), two hydroxy-M22 (M23 and M24), dihydroxy-M22 (M25), EAM-2201 N-pentanoic acid (M26), hydroxy-M26 (M27), dehydro-EAM-2201 (M28), hydroxy-M28 (M29), seven dihydroxy-M28 (M30-M36), and oxidative defluorinated hydroxy-M28 (M37). Multiple CYPs, including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2, 3A4, and 3A5, were involved in the metabolism of EAM-2201. In conclusion, EAM-2201 is extensively metabolized by CYPs and its metabolites can be used as an indicator of EAM-2201 abuse.

Original language	English
Pages (from-to)	50-58
Number of pages	9
Journal	Journal of Pharmaceutical and Biomedical Analysis
Volume	119
DOIs	https://doi.org/10.1016/j.jpba.2015.11.023
State	Published - 5 Feb 2016

Bibliographical note

Funding Information:
This work was supported by Supreme Prosecutors’ Office of Korea and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015M3A9E1028325).

Publisher Copyright:
© 2015 Elsevier B.V.

Keywords

Cytochrome P450
EAM-2201
Human liver microsomes
In vitro metabolism
LC-HRMS
Synthetic cannabinoid

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10.1016/j.jpba.2015.11.023

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@article{8024ddd8bc7245269bbe5af0d53cb593,

title = "In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s",

abstract = "In vitro metabolism of a new synthetic cannabinoid, EAM-2201, has been investigated with human liver microsomes and major cDNA-expressed cytochrome P450 (CYP) isozymes using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Incubation of EAM-2201 with human liver microsomes in the presence of NADPH resulted in the formation of 37 metabolites, including nine hydroxy-EAM-2201 (M1-M9), five dihydroxy-EAM-2201 (M10-M14), dihydrodiol-EAM-2201 (M15), oxidative defluorinated EAM-2201 (M16), two hydroxy-M16 (M17 and M18), three dihydroxy-M16 (M19-M21), N-dealkyl-EAM-2201 (M22), two hydroxy-M22 (M23 and M24), dihydroxy-M22 (M25), EAM-2201 N-pentanoic acid (M26), hydroxy-M26 (M27), dehydro-EAM-2201 (M28), hydroxy-M28 (M29), seven dihydroxy-M28 (M30-M36), and oxidative defluorinated hydroxy-M28 (M37). Multiple CYPs, including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2, 3A4, and 3A5, were involved in the metabolism of EAM-2201. In conclusion, EAM-2201 is extensively metabolized by CYPs and its metabolites can be used as an indicator of EAM-2201 abuse.",

keywords = "Cytochrome P450, EAM-2201, Human liver microsomes, In vitro metabolism, LC-HRMS, Synthetic cannabinoid",

author = "Kim, {Ju Hyun} and Kim, {Hee Seung} and Kong, {Tae Yeon} and Lee, {Joo Young} and Kim, {Jin Young} and In, {Moon Kyo} and Lee, {Hye Suk}",

note = "Funding Information: This work was supported by Supreme Prosecutors{\textquoteright} Office of Korea and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015M3A9E1028325). Publisher Copyright: {\textcopyright} 2015 Elsevier B.V.",

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doi = "10.1016/j.jpba.2015.11.023",

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AU - Kim, Ju Hyun

AU - Kim, Hee Seung

AU - Kong, Tae Yeon

AU - Lee, Joo Young

AU - Kim, Jin Young

AU - In, Moon Kyo

AU - Lee, Hye Suk

N1 - Funding Information: This work was supported by Supreme Prosecutors’ Office of Korea and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015M3A9E1028325). Publisher Copyright: © 2015 Elsevier B.V.

PY - 2016/2/5

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N2 - In vitro metabolism of a new synthetic cannabinoid, EAM-2201, has been investigated with human liver microsomes and major cDNA-expressed cytochrome P450 (CYP) isozymes using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Incubation of EAM-2201 with human liver microsomes in the presence of NADPH resulted in the formation of 37 metabolites, including nine hydroxy-EAM-2201 (M1-M9), five dihydroxy-EAM-2201 (M10-M14), dihydrodiol-EAM-2201 (M15), oxidative defluorinated EAM-2201 (M16), two hydroxy-M16 (M17 and M18), three dihydroxy-M16 (M19-M21), N-dealkyl-EAM-2201 (M22), two hydroxy-M22 (M23 and M24), dihydroxy-M22 (M25), EAM-2201 N-pentanoic acid (M26), hydroxy-M26 (M27), dehydro-EAM-2201 (M28), hydroxy-M28 (M29), seven dihydroxy-M28 (M30-M36), and oxidative defluorinated hydroxy-M28 (M37). Multiple CYPs, including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2, 3A4, and 3A5, were involved in the metabolism of EAM-2201. In conclusion, EAM-2201 is extensively metabolized by CYPs and its metabolites can be used as an indicator of EAM-2201 abuse.

AB - In vitro metabolism of a new synthetic cannabinoid, EAM-2201, has been investigated with human liver microsomes and major cDNA-expressed cytochrome P450 (CYP) isozymes using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Incubation of EAM-2201 with human liver microsomes in the presence of NADPH resulted in the formation of 37 metabolites, including nine hydroxy-EAM-2201 (M1-M9), five dihydroxy-EAM-2201 (M10-M14), dihydrodiol-EAM-2201 (M15), oxidative defluorinated EAM-2201 (M16), two hydroxy-M16 (M17 and M18), three dihydroxy-M16 (M19-M21), N-dealkyl-EAM-2201 (M22), two hydroxy-M22 (M23 and M24), dihydroxy-M22 (M25), EAM-2201 N-pentanoic acid (M26), hydroxy-M26 (M27), dehydro-EAM-2201 (M28), hydroxy-M28 (M29), seven dihydroxy-M28 (M30-M36), and oxidative defluorinated hydroxy-M28 (M37). Multiple CYPs, including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2, 3A4, and 3A5, were involved in the metabolism of EAM-2201. In conclusion, EAM-2201 is extensively metabolized by CYPs and its metabolites can be used as an indicator of EAM-2201 abuse.

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KW - Human liver microsomes

KW - In vitro metabolism

KW - LC-HRMS

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DO - 10.1016/j.jpba.2015.11.023

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C2 - 26641707

AN - SCOPUS:84948411744

SN - 0731-7085

VL - 119

SP - 50

EP - 58

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

ER -

In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s

Abstract

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Keywords

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