Forensic Toxicology

, Volume 30, Issue 2, pp 87–97 | Cite as

Oxidation of lysergic acid diethylamide (LSD) by peroxidases: a new metabolic pathway

  • Melissa M. Gomes
  • Felipe A. Dörr
  • Luiz H. Catalani
  • Ana Campa
Original Article


Lysergic acid diethylamide (LSD) is a potent hallucinogen that is primarily metabolized to 2-oxo-3-hydroxy-LSD (O-H-LSD) and N-desmethyl-LSD (nor-LSD) by cytochrome P450 complex liver enzymes. Due to its extensive metabolism, there still is an interest in the identification of new metabolites and new routes of its metabolism in humans. In the present study, we investigated whether LSD could be a substrate for horseradish peroxidase or myeloperoxidase (MPO). Using liquid chromatography coupled to UV detection and electrospray ionization mass spectrometry (LC-UV–ESI–MS), we found that both peroxidases were capable of metabolizing LSD to the same compounds that have been observed in vivo (i.e., O-H-LSD and nor-LSD). In addition, we found another major metabolite, N,N-diethyl-7-formamido-4-methyl-6-oxo-2,3,4,4a,5,6-hexahydrobenzo[f]quinoline-2-carboxamide (FOMBK), which is an opened indolic ring compound. Hydrolysis of FOMBK led to the deformylated compound 7-amino-N,N-diethyl-4-methyl-6-oxo-2,3,4,4a,5,6-hexahydrobenzo[f]quinoline-2-carboxamide. The reactions of LSD with the peroxidases were chemiluminescent and sensitive to inhibition by reactive oxygen scavengers, which indicated that the classic peroxidase cycle is involved in this new alternative metabolic pathway. Considering that MPO is abundant in immune cells and also present in the central nervous system, the degradation pathway described in this study suggests a possible route of LSD metabolism that may occur concurrently with the in vivo reaction catalyzed by the cytochrome P450 system.


Horseradish peroxidase Indole compounds Lysergic acid diethylamide LSD metabolism Myeloperoxidase Neutrophils Leukocytes 







Collision induced dissociation


Central nervous system




Electrospray ionization




Hydrogen peroxide


Horseradish peroxidase




Liquid chromatography-UV detection–electrospray ionization–mass spectrometry


Lysergic acid diethylamide




Mass-to-charge ratio




Superoxide anion




Phorbol 12-myristate 13-acetate


Reactive oxygen species


Superoxide dismutase





The authors thanks the Sao Paulo Research Foundation (FAPESP, Sao Paulo) and the National Counsel of Technological and Scientific Development (CNPq, Brasília).


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Copyright information

© Japanese Association of Forensic Toxicology and Springer 2012

Authors and Affiliations

  • Melissa M. Gomes
    • 1
  • Felipe A. Dörr
    • 1
  • Luiz H. Catalani
    • 2
  • Ana Campa
    • 1
  1. 1.Department of Clinical Chemistry and Toxicology, Faculty of Pharmaceutical SciencesUniversity of São PauloSão PauloBrazil
  2. 2.Department of Fundamental Chemistry, Chemistry InstituteUniversity of São PauloSão PauloBrazil

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