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Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS

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Abstract

The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high binding affinity at the peripheral cannabinoid receptor CB2, has been studied. A total of 22 metabolites were identified and structurally characterized. The metabolites are products of: 1) monohydroxylation on the naphthalene ring (m/z 344, M20 and M21), indole ring (m/z 344, M17 and M18), or the N-alkyl group (m/z 344, M14); 2) arene oxidation leading to dihydrodiols (m/z 362, M12 and M15); 3) dihydroxylation on the naphthalene ring (m/z 360, M7) or indole ring (m/z 360, M13), resulting from a combination of monohydroxylations on both the naphthalene and indole rings (m/z 360, M16), or a combination of monohydroxylations on the naphthalene ring and on the N-propyl group (m/z 360, M9); 4) trihydroxylation (m/z 378, M1, M3, M4, M6, and M10); 5) N-dealkylation (m/z 286, M19); 6) N-dealkylation and monohydroxylation on the naphthalene ring (m/z 302, M11); 7) N-dealkylation and dihydrodiol formation from arene oxidation (m/z 320, M2 and M5); 8) dehydrogenation after monohydroxylation on the N-alkyl group (m/z 326, M22); 9) dehydrogenation and monohydroxylation on the indole ring (m/z 342, M8).

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Authors and Affiliations

  1. Department of Chemistry, Xavier University of Louisiana, New Orleans, LA, 70125, USA

    Qiang Zhang, Peng Ma & Guangdi Wang

  2. Department of Chemistry, University of New Orleans, New Orleans, LA, 70148, USA

    Richard B. Cole

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  1. Qiang Zhang
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  2. Peng Ma
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  3. Richard B. Cole
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  4. Guangdi Wang
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Correspondence to Guangdi Wang.

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Zhang, Q., Ma, P., Cole, R.B. et al. Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS. Anal Bioanal Chem 386, 1345–1355 (2006). https://doi.org/10.1007/s00216-006-0717-6

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  • DOI: https://doi.org/10.1007/s00216-006-0717-6

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