Drug Testing and Analysis
September 20, 2013
Tomás Herraiz, Simon D. Brandt
25 citations
5-(2-Aminopropyl)indole (5-IT), a psychoactive compound linked to fatal and non-fatal intoxications in Europe, was tested for its effect on human monoamine oxidase (MAO) enzymes. Using kynuramine as a substrate, 5-IT selectively, competitively, and reversibly inhibited MAO-A with an IC50 of 1.6 μM and a Ki of 0.25 μM, while showing no inhibition of MAO-B up to 500 μM. Compared to established inhibitors, 5-IT was less potent than clorgyline (IC50 16 nM) and harmaline (20 nM) but more potent than toloxatone (6.7 μM) and moclobemide (>500 μM). This MAO-A inhibition suggests 5-IT may contribute to serotonergic toxicity, though further research is needed.
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.
Drug Testing and Analysis
August 15, 2016
Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh et al.
23 citations
Mexedrone, a derivative of mephedrone that appeared in 2015, was synthesized and analytically characterized. It was a weak non-selective uptake blocker at dopamine, norepinephrine, and serotonin transporters with IC50 values in the low micromolar range, and lacked releasing activity at dopamine and norepinephrine transporters but showed weak releasing activity at serotonin transporters (EC50 = 2.5 μM). Its isomer, N-methoxymephedrone, acted as a weak uptake blocker and a fully efficacious substrate-type releasing agent across all three transporters with EC50 values in the low micromolar range. A synthesis by-product, α-chloromethylmephedrone, was inactive in all assays.
Drug Testing and Analysis
August 30, 2016
Michael Collins, Christopher Donnelly, Shane Cameron et al.
21 citations
A red liquid seized by Australian authorities as a suspected MDMA precursor was identified as N-tert.-butoxycarbonyl-MDMA (t-BOC-MDMA), a derivative that can be converted to MDMA under acidic conditions. In simulated gastric juice, most t-BOC-MDMA converted to MDMA within 305 minutes, suggesting it could act as a pro-drug in the body. Similar t-BOC derivatives of methamphetamine, pseudoephedrine, and mephedrone were also prepared. The appearance of such derivatives on the drug market warrants monitoring.
Drug Testing and Analysis
April 2, 2013
Jason Wallach, Giorgia de Paoli, Adeboye Adejare et al.
21 citations
Six new psychoactive substances related to PCP and ketamine were synthesized and analyzed: three substituted 1-(1-phenylcyclohexyl)piperidines (3-MeO-, 4-MeO-, and 3-Me-PCP) and three substituted 1-(1-phenylcyclohexyl)pyrrolidine analogues (3-MeO-, 4-MeO-, and 3-Me-PCPy). Mass spectrometry, chromatography, infrared, and NMR spectroscopy characterized all six compounds and their intermediates. Solvent and protonation effects on NMR spectra were examined. Isomeric 3-MeO- and 4-MeO-PCP and PCPy analogues could be distinguished by mass spectrometry. Gas chromatography caused notable degradation of 4-MeO-substituted analytes, especially hydrochloride salts, producing a 1-phenylcyclohex-1-ene nucleus; this degradation was less pronounced with 3-MeO isomers, likely due to para-methoxy group resonance facilitating amine elimination.
Drug Testing and Analysis
August 9, 2012
Manuela Pellegrini, Maria Concetta Rotolo, Emilia Marchei et al.
21 citations
A liquid chromatography–tandem mass spectrometry method was developed to rapidly measure psilocybin and psilocin in Psilocybe sclerotia, known as magic truffles. After a simple methanol extraction, the alkaloids were separated on a reversed-phase column and detected using electrospray ionization tandem mass spectrometry. The method was linear over the calibration range with correlation coefficients above 0.99, detection limits of 0.3 µg per 100 mg, and quantification limits of 1 µg per 100 mg. Only psilocybin was found in the examined sclerotia, with concentrations ranging from 59.3 to 167.8 µg per 100 mg of fresh material.
Drug Testing and Analysis
November 27, 2021
Simon D. Brandt, Pierce V. Kavanagh, Folker Westphal et al.
19 citations
A new LSD derivative called 1-valeroyl-LSD (1V-LSD, or "Valerie") has appeared on the online market. It is a higher homolog of earlier derivatives like ALD-52, 1P-LSD, and 1B-LSD. The study analytically characterized 1V-LSD using mass spectrometry, chromatography, NMR, and Raman spectroscopy. In mice, 1V-LSD induced a head-twitch response, a behavioral proxy for human hallucinogenic effects, in a dose-dependent manner. Its median effective dose was 373 nmol/kg, about a third the potency of LSD (ED50 = 132.8 nmol/kg). 1V-LSD likely acts as a prodrug that is hydrolyzed to LSD, but further studies on its biotransformation and receptor pharmacology are needed.
Drug Testing and Analysis
July 5, 2016
Marcos Tascón, Fernando Benavente, Nora M. Vizioli et al.
18 citations
The β-carboline alkaloids of the harmala group (HAlks), found in plants like Peganum harmala (Syrian rue) and Banisteriopsis caapi, act as reversible monoamine oxidase type A inhibitors (MAOIs). Their levels in natural sources vary greatly, limiting clinical use and leading to recreational or ritual use, such as in Ayahuasca. This work presents a fast, simple, and robust method using capillary electrophoresis with UV detection to simultaneously quantify six common HAlks: harmine, harmaline, harmol, harmalol, harmane, and norharmane. The method was applied to analyze P. harmala seed infusion, detecting harmaline, harmine, and harmol. Validation across three instruments showed transferability and comparable performance.
Drug Testing and Analysis
October 20, 2014
Gavin McLaughlin, Noreen Morris, Pierce V. Kavanagh et al.
18 citations
A newly emerged psychoactive substance, 3,4-methylenedioxy-4-methylaminorex (MDMAR), was synthesized and characterized. Analysis of vendor-sourced MDMAR found it to be predominantly the cis-isomer (90%), which could artificially convert to the trans-isomer under certain liquid chromatography conditions. Both MDMAR isomers, along with cis- and trans-4,4'-DMAR, were more potent than MDMA in releasing dopamine and norepinephrine in rat brain tissue. While cis-4,4'-DMAR, cis-MDMAR, and trans-MDMAR fully released serotonin, trans-4,4'-DMAR acted as a serotonin uptake blocker. The high potency of these analogues at monoamine transporters may indicate potential for serious side-effects at high doses.
Drug Testing and Analysis
November 21, 2018
Katharina Elisabeth Grafinger, Andreas Wilke, Stefan König et al.
15 citations
A fungus, Cunninghamella elegans, can mimic human drug metabolism and was tested on four tryptamines: DMT, 4-HO-MET, 5-MeO-DALT, and 5-MeO-MiPT. After 72 hours of incubation, the fungus performed key biotransformation steps like hydroxylation, N-oxide formation, carboxylation, deamination, and demethylation. On average, 63% of phase I metabolites previously reported in the literature were also produced by C. elegans, along with some unique metabolites. The findings suggest C. elegans is a useful complementary model for studying the metabolism of natural and synthetic tryptamines, especially given the lack of pharmacological data for new psychoactive substances.
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.
Drug Testing and Analysis
July 1, 2010
Simon D. Brandt, Sharon A. Moore, Sally Freeman et al.
14 citations
An impurity profile was established for a synthetic route to the hallucinogen N,N-dimethyltryptamine (DMT) using reductive amination of tryptamine with formaldehyde and reduction by sodium cyanoborohydride. Seven compounds were detected and quantified, including DMT and several byproducts. Replacing sodium cyanoborohydride with sodium borohydride almost exclusively produced tetrahydro-β-carboline instead of DMT. Detection limits ranged from 21.5 to 87.7 ng mL⁻¹, and quantification limits from 24.6 to 88.3 µg mL⁻¹, with linearity from 20.8 to 980 µg mL⁻¹. The method is useful for forensic and pharmaceutical analysis of DMT.
Drug Testing and Analysis
July 3, 2018
Katharina Elisabeth Grafinger, Katja Stahl, Andreas Wilke et al.
13 citations
The metabolism of three hallucinogenic phenethylamines—25D-NBOMe, 25E-NBOMe, and 25N-NBOMe—was investigated using pooled human liver microsomes (pHLM) and the fungus Cunninghamella elegans. In pHLM, 36, 26, and 24 phase I metabolites were identified for 25D-NBOMe, 25E-NBOMe, and 25N-NBOMe, respectively; in C. elegans, 14, 11, and 9 metabolites were found. Major biotransformation steps included oxidative deamination, N-dealkylation, O-demethylation, hydroxylation, and oxidation of alcohols. Unique metabolites included N-oxide and hydroxylamine derivatives, reported for the first time for NBOMe compounds. C. elegans produced all main biotransformation steps observed in human microsomes, suggesting its potential as a model for studying new psychoactive substances.
Drug Testing and Analysis
September 11, 2015
Jason Wallach, Tristan Colestock, Brian Cicali et al.
13 citations
Fifteen N-alkyl-arylcyclohexylamines, including compounds related to the dissociative substances 3-MeO-PCP, 3-MeO-PCE, and 3-MeO-PCPr, were synthesized and characterized. Analytical methods such as gas chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy were used. Positional isomers of methoxy-substituted arylcyclohexylamines were readily distinguishable under various analytical conditions. The work provides previously unreported analytical data to aid in identifying newly emerging research chemicals.
Drug Testing and Analysis
March 31, 2015
Jochen Gartz, Georg Wiedemann
13 citations
A new species of psychoactive mushroom, Psilocybe germanica, is described from Germany. It grows on wood chips and bark mulch in parks, fruits from September to December, and turns deep blue when bruised or aged. Chemical analysis showed it contains high levels of psilocybin and baeocystin but no psilocin, distinguishing it from other wood-loving Psilocybe species. Its stipe has a unique joint-like thickening near the cap, and its cap is not striate or translucent when wet. The authors suggest that, like Psilocybe cyanescens, this species may become widespread due to the increasing use of wood mulch in landscaping.
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
July 1, 2020
Nicholas V. Cozzi, Paul F. Daley
12 citations
A slightly modified Speeter–Anthony synthesis produced DMT hemifumarate with over 99.9% purity, meeting regulatory standards for human intravenous administration. Aluminum hydride generated in situ from lithium aluminum hydride was used for the first time to reduce an intermediate to DMT, and a quench protocol yielded exceptionally pure free base DMT. The final salt was analyzed by multiple techniques including X-ray powder diffraction, NMR, GC–MS, and HPLC. No significant impurities or residual solvents were detected. The work supports planned clinical trials of DMT for major depressive disorder.
Drug Testing and Analysis
October 31, 2019
Kateřina Hájková, Bronislav Jurásek, Jan Čejka et al.
12 citations
Deschloroketamine, a ketamine analog sold illicitly since 2015 and sometimes misrepresented as ketamine, has potential antidepressant properties. A metabolomics study used liquid chromatography–high-resolution mass spectrometry and a validated multiple reaction monitoring method to track its metabolites in urine, serum, and brain tissue. Key metabolites—trans-dihydrodeschloroketamine, cis- and trans-dihydronordeschloroketamine, and nordeschloroketamine—were synthesized and used as standards. In serum, nordeschloroketamine and deschloroketamine concentrations ranged from 0.5 to 860 ng/mL; in brain tissue, they ranged from 0.5 to 4700 ng/g. The quantification methods showed intra-day accuracy of 80–125% and precision averaging 3–7%.
Drug Testing and Analysis
October 23, 2020
P. Kintz, A. Ameline, J. Raul
10 citations
Hair tests can detect long-term drug use, but external contamination risks false positives. Advanced analytical equipment now allows precise quantification of drugs in hair at picogram per milligram levels. In a family law case, DMT was found in the hair of a partner of a repetitive DMT smoker at 4 to 13 pg/mg across six 1-cm segments, with concentrations increasing from proximal to distal ends. This pattern and low concentrations indicate environmental contamination rather than ingestion, as older hair had longer contact with the drug. Even after decontamination, environmental drugs can remain bound to hair, enabling documentation of exposure.
Drug Testing and Analysis
January 1, 2012
Simon D. Brandt, Ruchanok Tearavarich, Nicola M. Dempster et al.
10 citations
Thirteen new tryptamine derivatives were synthesized and analyzed to provide reference data for forensic and clinical identification. Using NMR and mass spectrometry, the compounds were characterized and distinguished from each other and from related substances. Key mass spectral fragments were identified, including an iminium ion and indole-related ions at specific mass-to-charge ratios. The work extends earlier research on similar compounds and supplies analytical standards that can help professionals identify these substances before they cause adverse health effects.
Drug Testing and Analysis
December 29, 2010
Ruchanok Tearavarich, Viwat Hahnvajanawong, Nicola M. Dempster et al.
10 citations
Twelve novel 5-ethoxy-N,N-dialkyl-tryptamines and their deuterated counterparts were synthesized using a microwave-accelerated reduction step that took 5 minutes in tetrahydrofuran at 150 °C. The resulting 24 tryptamines were characterized by nuclear magnetic resonance spectroscopy and gas chromatography ion trap mass spectrometry, revealing differential fragmentation of side-chain-related iminium ions. These compounds are intended as internal standards for bioanalytical and pharmacological assays, aiding identification of novel tryptamines from non-traditional sources, and are of immediate value in forensic, research, and public health contexts.
Drug Testing and Analysis
April 30, 2019
Michael Dybek, Jason Wallach, Pierce V. Kavanagh et al.
9 citations
Six possible racemic isomers of the research chemical fluorolintane (2-F-DPPy) were synthesized and characterized. The isomers differ by the position of a fluorine substituent on the phenyl or benzyl ring of the 1,2-diarylethylamine structure. Using mass spectrometry, chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy, each isomer was distinguishable. A tandem mass spectrometry method analyzing the [M + H – HF]+ species produced distinct product ions for all six substances, aiding identification of positional isomers that pose challenges for stakeholders confronting new psychoactive substances.
Drug Testing and Analysis
March 26, 2019
Stefan W. Toennes, David J. Schneider, Werner Pogoda et al.
9 citations
The pharmacokinetics of 4-fluoroamphetamine (4-FA) in humans resemble those of amphetamine, with peak serum concentrations occurring about 2 hours after ingestion and an elimination half-life of roughly 8-9 hours, though this varies widely (5.5-16.8 hours). After a 100 mg dose, median maximum serum concentration was 195 ng/mL (range 155-316 ng/mL). Concentrations in oral fluid were higher than in serum, especially during the first 3 hours, likely due to oral contamination. Serum concentrations observed in forensic cases matched those in the study, suggesting recreational doses are similar, but such doses may already cause prominent adverse effects and life-threatening consequences.
Drug Testing and Analysis
April 19, 2018
Gavin McLaughlin, Michael H. Baumann, Pierce V. Kavanagh et al.
8 citations
Two new psychoactive substances, 4-methylphenmetrazine (4-MPM) and 3-methylphenmetrazine (3-MPM), have appeared on the recreational drug market following the earlier emergence of 3-fluorophenmetrazine. Analytical characterization of vendor samples confirmed the presence of 4-MPM in two samples and 3-MPM in one sample. In vitro transporter assays using rat brain synaptosomes tested the isomers' ability to inhibit uptake or stimulate release of dopamine, norepinephrine, and serotonin. The findings suggest that 2-MPM and 3-MPM will exhibit stimulant properties similar to phenmetrazine, whereas 4-MPM may display entactogen properties more similar to MDMA. Combining test purchases, analytical characterization, targeted synthesis, and pharmacological evaluation provides an effective approach for generating data on emerging substances.
Drug Testing and Analysis
August 15, 2013
Leslie A. King, István Ujváry, Simon D. Brandt
8 citations
The term 'derivative' has a precise but context-dependent meaning in chemistry, yet it appears widely in drug legislation without clear definition. Many assume only first-order derivatives—substances made in one reaction step—are covered, but this excludes substances like 2-carbomethoxytropinone, convertible to cocaine in multiple steps, which courts have ruled as controlled. The US Drug Enforcement Administration successfully argued in 1986 that buprenorphine, requiring six or more steps from thebaine, is a derivative. This ambiguity leaves the legal status of substances like 2-bromo-LSD uncertain. The authors suggest that unless qualified, the term should be avoided in future legislation.