Drug Testing and Analysis
May 1, 2023
Linhao Xu, Xinze Liu, Zixuan Song et al.
3-Methoxyeticyclidine (3-MeO-PCE), a substance related to phencyclidine (PCP), binds more strongly to NMDA receptors than PCP and has been linked to fatal overdoses. Using zebrafish and human liver microsomes, researchers identified 14 metabolites of 3-MeO-PCE through metabolic pathways including hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, and conjugation. Urine samples from known consumers revealed 3-MeO-PCE and three metabolites. The hydroxylation product, M2, is recommended as a biomarker to confirm 3-MeO-PCE intake in clinical and forensic settings.
Drug Testing and Analysis
April 20, 2020
A. Davidsen, M. Mardal, S. Johansen et al.
The phencyclidine (PCP) analogue 3-HO-PCP, a potent dissociative new psychoactive substance, was detected in a law enforcement seizure and forensic samples in Denmark. Its toxicokinetic properties were investigated for the first time. The unbound fraction in plasma was 0.72 ± 0.09. Four in vitro metabolites were identified after incubation with human hepatocytes; in vivo, the O-sulphate-conjugated metabolite was not detected, and the N-dealkylated-COOH metabolite was the main metabolite in deconjugated urine. In blood and brain, 3-HO-PCP and its O-glucuronidated metabolite were the primary analytical targets. Drug levels in blood were 0.013 mg/kg in a living subject and 0.095 mg/kg in a deceased subject. Post-mortem brain concentration was 0.16 mg/kg, 1.5-fold higher than in post-mortem blood.
Drug Testing and Analysis
April 1, 2020
Elias Lützen, Michael Holtkamp, Imke Stamme et al.
Blotter papers sold as LSD sometimes contain cheaper phenethylamine derivatives like 25I-NBOMe and 25C-NBOMe, which can cause severe intoxication. Using three imaging techniques and liquid chromatography-mass spectrometry, the manufacturing process was elucidated. Micro x-ray fluorescence was the fastest and cheapest method for identifying the compounds, requiring no sample preparation. Laser ablation-inductively coupled plasma-optical emission spectroscopy provided three-dimensional elemental information, supporting the conclusion that manufacturers spray the compounds onto the paper. Matrix assisted laser desorption ionization-mass spectrometry imaging showed the molecular distribution of both analytes. Quantitative results revealed a heterogeneous distribution of the drugs on the blotter paper, implying an inherent risk of overdosing for consumers.
Drug Testing and Analysis
January 8, 2019
S. Allard, Pierre-Marie Allard, I. Morel et al.
Untargeted toxicological screening faces challenges due to the vast number of molecules and new psychoactive substances (NPS). Molecular networking, a bioinformatic tool that organizes MS/MS data by spectral similarity without requiring prior knowledge of chemical composition, was applied to three clinical and forensic cases: a death by self-injection, a drug-facilitated assault, and an intoxication case. This approach allowed exploration and organization of spectral data, enabling structural information propagation and sample-to-sample comparison. The work demonstrates that molecular networking can complement conventional methods for identifying xenobiotics and elucidating NPS metabolism.
Drug Testing and Analysis
May 1, 2017
Ariane Wohlfarth, Markus Roman, Mikael Andersson et al.
The hallucinogenic drugs 25C-NBOMe and 25I-NBOMe are primarily broken down in the body by O-demethylation, followed by O-di-demethylation and hydroxylation. All methoxy groups could be demethylated; hydroxylation occurred mainly on the NBOMe ring. Phase I metabolites were extensively conjugated with glucuronic acid and sulfate in human urine. Specific and abundant urine targets for detecting 25C-NBOMe are 5'-desmethyl 25C-NBOMe, 25C-NBOMe, and 5-hydroxy 25C-NBOMe; for 25I-NBOMe, they are 2' and 5'-desmethyl 25I-NBOMe and hydroxy 25I-NBOMe. These findings can aid clinical and forensic laboratories in developing analytical methods and interpreting results.
Drug Testing and Analysis
May 1, 2017
Line Marie Nielsen, Niels Bjerre Holm, Sebastian Leth-Petersen et al.
The NBOMe compounds, potent serotonin 5-HT2A receptor agonists used recreationally for their hallucinogenic effects, are metabolized primarily by specific cytochrome P450 enzymes. For 25I-NBOMe, CYP3A4 is the major enzyme involved; for 25I-NBOH, CYP2D6 is the major enzyme. 25I-NBOH also undergoes direct glucuronidation, which may reduce the impact of CYP2D6 genetic variation. The intrinsic clearance values were 70.1 mL/min/kg for 25I-NBOMe and 118.7 mL/min/kg for 25I-NBOH. Users of 25I-NBOMe may face drug-drug interactions if taken with a strong CYP3A4 inhibitor. Metabolites included hydroxylation, O-demethylation, N-dealkylation, and dehydrogenation products.