Analytical and Bioanalytical Chemistry
June 24, 2015
Achim T. Caspar, Andreas G. Helfer, Julian A. Michely et al.
69 citations
25I-NBOMe, a potent hallucinogenic drug that activates 5-HT2A receptors, is extensively metabolized in rats. After administration to male Wistar rats, 68 metabolites were identified in urine using liquid chromatography-high-resolution tandem mass spectrometry. The main metabolic pathways include O-demethylation, O,O-bis-demethylation, hydroxylation, and combinations, followed by glucuronidation and sulfation. Detection of intake is possible through metabolites using LC-MS methods but not by GC-MS standard urine screening. Initial tests indicate that CYP1A2 and CYP3A4 are involved in hydroxylation, while CYP2C9 and CYP2C19 mediate O-demethylation, suggesting potential drug-drug interactions.
Clinical Chemistry
June 30, 2017
Marilyn A. Huestis, Simon D. Brandt, Suman Rana et al.
42 citations
Novel psychoactive substances (NPS) have been present in clinical and forensic toxicology for over a century, with early examples including heroin, LSD, MDMA, and GHB. After synthetic cannabinoids emerged in the early 2000s, hundreds of synthetic cathinones, benzodiazepines, and opioids rapidly appeared. Toxicology laboratories, once focused on a narrow range of compounds, now face potent fentanyl derivatives mixed with or substituted for heroin, causing rising fatalities. Labs struggle to detect short-lived drug analogs, unknown urinary metabolites, and lack reference standards. Four international experts discuss what drove the global NPS market, how toxicology laboratories can address these challenges, and how public health and law enforcement can reduce NPS-related morbidity and mortality.
Journal of Pharmaceutical and Biomedical Analysis
May 28, 2019
Christina Grumann, Kerstin Henkel, Alexander Stratford et al.
27 citations
1-propionyl-LSD (1P-LSD), an uncontrolled derivative of LSD, requires sensitive detection methods due to its high potency. A validated LC-MS/MS method quantified 1P-LSD and LSD in urine and serum with a calibration range of 0.015-0.4 ng mL⁻¹ and limits of detection and quantification at 0.005 and 0.015 ng mL⁻¹, respectively. Stability tests showed 1P-LSD remained stable in samples stored at -20 °C, 5 °C, or room temperature for up to five days, but LSD formed at room temperature (up to 21% in serum), likely from enzymatic hydrolysis. Sodium fluoride prevented this conversion. In an intoxication case, only LSD was detected: 0.51 ng mL⁻¹ in urine and 3.4 ng mL⁻¹ in serum, suggesting rapid in-vivo hydrolysis of 1P-LSD to LSD.
Drug Testing and Analysis
May 16, 2020
Christina Grumann, Kerstin Henkel, Simon D. Brandt et al.
23 citations
1P-LSD, a non-controlled alternative to LSD, acts as a prodrug that converts almost entirely into LSD in the human body. In two volunteers, oral and intravenous doses of 100 μg 1P-LSD were administered. After oral intake, only LSD was detected in serum and urine, with a terminal elimination half-life of about 6.4 hours. Intravenous 1P-LSD was detectable for only a few hours, while LSD persisted much longer. The bioavailability of LSD from oral 1P-LSD was nearly 100%. Subjective drug effects and altered states of consciousness scores were comparable to those from LSD, supporting the prodrug hypothesis. Oral administration produced higher 5D-ASC scores than intravenous.
Clinical toxicology (Philadelphia, Pa.)
September 1, 2017
Maren Hermanns-Clausen, Verena Angerer, Josephine Kithinji et al.
22 citations
A 42-year-old man accidentally ingested 25I-NBOMe, a potent hallucinogenic drug, after taking a sip of pediatric analgesic syrup that had been refilled with a self-made solution of the drug in ethanol. Within 30 minutes he became restless, and in the emergency department he showed dilated pupils, heavy sweating, disorientation, agitation, and later severe agitation, coenesthesia, and complex hallucinations. Blood tests at admission detected 25I-NBOMe (34 ng/mL), its metabolite 2C-I (12 ng/mL), and 25I-NBOH (<1 ng/mL). The syrup contained 2800 μg/mL of 25I-NBOMe. Symptoms resolved after six hours without complications. The presence of 2C-I 50 minutes after intake suggests rapid metabolic breakdown of 25I-NBOMe via first-pass metabolism.
Drug Testing and Analysis
May 7, 2022
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
14 citations
The lysergamide 1P-AL-LAD is characterized and tested in vitro and in mice. In pooled human liver microsomes, 1P-AL-LAD converts to AL-LAD as the most abundant metabolite, supporting the idea that it acts as a prodrug. Fourteen metabolites are detected, including hydroxylation and deacylation products. In mice, 1P-AL-LAD produces a dose-dependent increase in head twitch response, a behavioral proxy for human hallucinogenic effects, with an inverted U-shaped dose-response curve. Its median effective dose is 491 nmol/kg, almost three times less potent than AL-LAD (174.9 nmol/kg). The prodrug mechanism likely explains its activity despite N1-substitution disrupting 5-HT2A receptor activation.
Journal of analytical toxicology
May 20, 2022
Hannes M Schwelm, Nicole Zimmermann, Tobias Scholl et al.
13 citations
The poison of the Colorado River toad (Incilius alvarius) contains a variety of psychoactive tryptamines, with 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) as the main component at an average concentration of 410,000 μg per gram of poison. Using multiple analytical methods, researchers identified nine tryptamine compounds, including 5-MeO-tryptamine and two positional isomers of hydroxylated MeO-DMT detected for the first time in this species. Concentrations of other tryptamines such as bufotenin (2,800 μg/g), 5-MeO-tryptamine (490 μg/g), 5-HO-N-methyltryptamine (270 μg/g), and DMT (250 μg/g) varied considerably between individual toad samples. These comprehensive reference data may assist forensic chemists in analyzing toad venom samples.
Drug Testing and Analysis
May 22, 2021
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
12 citations
Lysergic acid diethylamide (LSD) is a potent psychoactive substance of clinical interest, and its analogs, including N-methyl-N-isopropyl isomer (MIPLA), have appeared on the street market. This report describes analytical methods to differentiate MIPLA from LSD and the N-methyl-N-propyl isomer (LAMPA) under routine conditions. Gas chromatography-solid phase infrared spectroscopy was particularly helpful. GC-electron ionization-tandem mass spectrometry of the m/z 72 iminium ion distinguished the three isomers on mass spectral grounds alone. Derivatization with BSTFA improved GC separation. LC-Q-MS and in-source collision-induced dissociation differentiated MIPLA and LAMPA based on distinct m/z 239 ion ratios. An alternative LC-MS/MS method improved separation but LSD co-eluted with iso-LSD; comparing ion ratios at m/z 324.2 > 223.2 and 324.2 > 208.2 facilitated differentiation. Two blotters contained 180 and 186 μg MIPLA per blotter.
Drug testing and analysis
March 1, 2023
Pierce V Kavanagh, Folker Westphal, Benedikt Pulver et al.
7 citations
A new lysergamide, 1cP-AL-LAD, was analyzed using chromatographic, mass spectrometric, and spectroscopic methods. A powdered sample from an online vendor contained 17 impurities, including AL-LAD and 1P-AL-LAD (confirmed by reference standards) and tentatively identified compounds such as 1-acetyl-AL-LAD and oxidation products of the N6-allyl group and ergoline ring. The substance was also found in blotter paper samples sold online for recreational use. These findings provide analytical data for researchers interested in lysergamide chemistry.
Drug testing and analysis
September 1, 2024
Verena Angerer, Yasmin Schmid, Florian Franz et al.
6 citations
In six healthy volunteers, the new psychoactive substance MDAI at 3.0 mg/kg produced subjective effects comparable to 125 mg of MDMA, including increased blood pressure, but did not raise heart rate or body temperature. MDAI increased cortisol and prolactin levels, appeared in serum about 20 minutes after ingestion, and remained detectable for at least 4 days in serum and 6 days in urine. The drug was well tolerated. Further research is needed to evaluate whether MDAI might have medicinal applications.
Journal of pharmaceutical and biomedical analysis
March 15, 2024
Merja A Neukamm, Stefan Pollak, Vanessa Thoma et al.
5 citations
A 20-year-old man with prior hallucinogen experience died after sniffing an unknown amount of dipropyltryptamine, a hallucinogenic tryptamine similar to DMT but with longer duration. Within minutes he had visual hallucinations and apathy; two hours later he developed abdominal pain, collapsed, seized, and vomited. Despite resuscitation and hospital transport, he died 21 hours after consumption. Autopsy showed aspiration of gastric contents and brain edema from oxygen deprivation. Dipropyltryptamine concentrations were 210 ng/ml in antemortem serum, 110 ng/ml in postmortem cardiac blood, and 180 ng/ml in urine. Unlike typical tryptamine overdoses, there was no agitation, hyperthermia, or tachycardia. Death resulted indirectly from a high nasal dose.
Drug testing and analysis
February 1, 2024
Simon D Brandt, Pierce V Kavanagh, Folker Westphal et al.
5 citations
N-ethyl-N-isopropyllysergamide (EIPLA), an isomer of the psychedelic lysergamide ETH-LAD, shows LSD-like properties in preclinical tests. Mass spectrometry, chromatography, and NMR spectroscopy distinguished EIPLA from ETH-LAD by their structural features. Blotter extracts contained 96.9 ± 0.5 μg and 85.8 ± 2.8 μg of EIPLA base. In mice, EIPLA induced head-twitch responses (ED50 = 234.6 nmol/kg), about half the potency of LSD (ED50 = 132.8 nmol/kg), consistent with serotonergic psychedelic effects. Analytical data are provided to aid forensic and clinical identification.