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In vitro metabolic fate of nine LSD-based new psychoactive substances and their analytical detectability in different urinary screening procedures

  • Lea Wagmann
  • Lilian H. J. Richter
  • Tobias Kehl
  • Franziska Wack
  • Madeleine Pettersson Bergstrand
  • Simon D. Brandt
  • Alexander Stratford
  • Hans H. Maurer
  • Markus R. Meyer
Research Paper
Part of the following topical collections:
  1. Young Investigators in (Bio-)Analytical Chemistry

Abstract

The market of new psychoactive substances (NPS) is characterized by a high turnover and thus provides several challenges for analytical toxicology. The analysis of urine samples often requires detailed knowledge about metabolism given that parent compounds either may be present only in small amounts or may not even be excreted. Hence, knowledge of the metabolism of NPS is a prerequisite for the development of reliable analytical methods. The main aim of this work was to elucidate for the first time the pooled human liver S9 fraction metabolism of the nine d-lysergic acid diethylamide (LSD) derivatives 1-acetyl-LSD (ALD-52), 1-propionyl-LSD (1P-LSD), 1-butyryl-LSD (1B-LSD), N6-ethyl-nor-LSD (ETH-LAD), 1-propionyl-N6-ethyl-nor-LSD (1P-ETH-LAD), N6-allyl-nor-LSD (AL-LAD), N-ethyl-N-cyclopropyl lysergamide (ECPLA), (2′S,4′S)-lysergic acid 2,4-dimethylazetidide (LSZ), and lysergic acid morpholide (LSM-775) by means of liquid chromatography coupled to high-resolution tandem mass spectrometry. Identification of the monooxygenase enzymes involved in the initial metabolic steps was performed using recombinant human enzymes and their contribution confirmed by inhibition experiments. Overall, N-dealkylation and hydroxylation, as well as combinations of these steps predominantly catalyzed by CYP1A2 and CYP3A4, were found. For ALD-52, 1P-LSD, and 1B-LSD, deacylation to LSD was observed. The obtained mass spectral data of all metabolites are essential for reliable analytical detection particularly in urinalysis and for differentiation of the LSD-like compounds as biotransformations also led to structurally identical metabolites. However, in urine of rats after the administration of expected recreational doses and using standard urine screening approaches, parent drugs or metabolites could not be detected.

Keywords

Lysergamides NPS Metabolism Urinalysis LC-HRMS/MS 

Notes

Acknowledgments

The authors would like to thank Armin A. Weber and the Stiftelsen för Klinisk farmakologi & farmakoterapi for support.

Compliance with ethical standards

The studies have been approved by an ethics committee (Landesamt für Verbraucherschutz, Saarbrücken, Germany).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2018_1558_MOESM1_ESM.pdf (2.8 mb)
ESM 1 (PDF 2917 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lea Wagmann
    • 1
  • Lilian H. J. Richter
    • 1
  • Tobias Kehl
    • 1
  • Franziska Wack
    • 1
  • Madeleine Pettersson Bergstrand
    • 1
    • 2
    • 3
  • Simon D. Brandt
    • 4
  • Alexander Stratford
    • 5
  • Hans H. Maurer
    • 1
  • Markus R. Meyer
    • 1
  1. 1.Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS)Saarland UniversityHomburgGermany
  2. 2.Department of Laboratory Medicine, Division of Clinical PharmacologyKarolinska InstitutetStockholmSweden
  3. 3.Department of Laboratory Medicine, Division of Clinical ChemistryKarolinska InstitutetStockholmSweden
  4. 4.School of Pharmacy and Biomolecular SciencesLiverpool John Moores UniversityLiverpoolUK
  5. 5.Synex Synthetics BVMaastrichtThe Netherlands

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