Skip to content

Drug Testing and Analysis

ISSN 1942-7603

40 papers in the library · 1,486 citations · publishing 2010-2026

Papers

Investigating the ability of the microbial model Cunninghamella elegans for the metabolism of synthetic tryptamines

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.

Analytical profile, in vitro metabolism and behavioral properties of the lysergamide 1P‐AL‐LAD

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.

Characterization of the synthesis of N,N‐dimethyltryptamine by reductive amination using gas chromatography ion trap mass spectrometry

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.

In vitro phase I metabolism of three phenethylamines 25D‐NBOMe, 25E‐NBOMe and 25N‐NBOMe using microsomal and microbial models

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.

Discovery of a new caerulescent Psilocybe mushroom in Germany: Psilocybe germanica sp.nov.

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.

Separating the wheat from the chaff: Observations on the analysis of lysergamides LSD, MIPLA, and LAMPA

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.

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

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.

Human hair tests to document drug environmental contamination: Application in a family law case involving N,N-dimethyltryptamine.

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.

Enzyme‐assisted synthesis of the glucuronide conjugate of psilocin, an hallucinogenic component of magic mushrooms

Drug Testing and Analysis February 2, 2011 Takuji Shoda, Kiyoshi Fukuhara, Yukihiro Goda et al. 8 citations

An enzyme-assisted method produced psilocin glucuronide (PCG), a metabolite excreted in the urine of magic mushroom users. Using Aroclor 1254 pretreated rat liver microsomes, psilocin and the cofactor UDPGA were incubated for 20 hours. HPLC purification yielded 3.6 mg of PCG (19% yield). The structure was confirmed by mass spectrometry and NMR. The milligram amounts produced will enable direct identification and quantification of PCG in the urine of magic mushroom users.

Tentative identification of in vitro metabolites of O‐acetylpsilocin (psilacetin, 4‐AcO‐DMT) by UHPLC‐Q‐Orbitrap MS

Drug Testing and Analysis March 21, 2022 Wenya Zhai, Le Li, Junbo Zhao et al. 5 citations

4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT, psilacetin) is a synthetic psychedelic that may act as a precursor to psilocin, but its metabolism was poorly understood. Incubating 4-AcO-DMT with pooled human liver microsomes produced 15 metabolites: 12 from phase I and 3 from phase II reactions. Transformations included hydrolysis, hydroxylation, N-demethylation, oxidation, and glucuronic acid conjugation. The hydrolysis product was the most abundant. For forensic detection of 4-AcO-DMT use, the beta-hydroxylation metabolite (M2-1) is recommended as a biomarker. These findings may help predict in vivo metabolism and assist drug testing.

Special issue on illicit drugs

Drug Testing and Analysis September 1, 2011 Simon D. Brandt 5 citations

This special issue presents a variety of techniques and topics in illicit drug research, ranging from classic drugs like cocaine to internet drugs and new psychoactive substances. Raman spectroscopy is reviewed for non-destructive analysis of street drugs, including detection on fibers, fingerprints, banknotes, and in body fluids, as well as for detecting cocaine concealed in rum bottles down to 6% w/v solutions. Proton magnetic resonance spectroscopy at 3 Tesla can detect cocaine in wine bottles at 5 mM levels. Synthetic cathinones and other online-accessible drugs like GHB are reviewed for clinical effects and harm reduction. Internet products often have misleading labels; six out of seven products analyzed showed incorrect labeling.

N,N‐Diformylmescaline: A novel analogue of mescaline detected in Queensland

Drug Testing and Analysis October 17, 2022 Ryan Gallagher, Maddison G. Mclaughlin, Karen Blakey et al. 2 citations

A novel analogue of mescaline, N,N-diformylmescaline, was identified in two unrelated drug seizures in Australia. A three-step synthesis from 3,4,5-trimethoxyphenylacetic acid was developed, but purification was difficult because the compound degrades in solution. Analysis by LC–MS showed instability under acidic and basic conditions, breaking down first to N-formylmescaline and then to mescaline when dissolved in hydrochloric acid for an extended period, suggesting it may act as a prodrug for mescaline. The paper presents GC–MS, NMR, and FTIR data for the seized compound, along with synthesis details and stability studies.

Bioactivation and Metabolism of Amino Acid MDMA Prodrugs in Zebrafish Embryos, Human Liver S9, Whole Blood, and Microdosed Human Urine

Drug Testing and Analysis March 15, 2026 Simon K. Wellenberg, Lea Wagmann, Matthias D. Kroesen et al.

Amino acid prodrugs of MDMA—MDMA-tryptophan, MDMA-lysine, and MDMA-glycine—are cleaved to release MDMA in zebrafish embryos, human liver S9 fraction, and human urine after microdosing, but not in human blood under the tested conditions. MDMA-tryptophan follows a stepwise bioactivation pathway involving hydroxylation and N-dealkylation before amide cleavage, unlike the other prodrugs which convert directly. Known MDMA metabolites also form in zebrafish and liver systems. Unique urine screening targets appear only for MDMA-tryptophan; biomarkers for the other prodrugs are MDMA and its known metabolites. Further studies of human pharmacokinetic profiles are needed.

Identification and Analysis of Lysergic Acid Diethylamide Analogs, 4‐Benzoyl‐ N,N ‐Diethyl‐7‐Methyl‐4,6,6a,7,8,9‐Hexahydroindolo[4,3‐ fg ]quinoline‐9‐Carboxamide (1Bz‐LSD) and N , N ‐Diethyl‐7‐Methyl‐4‐(4‐(Trimethylsilyl)Benzoyl)‐4,6,6a,7,8,9‐Hexahydroindolo[4,3‐ fg ]quinoline‐9‐Carboxamide (1‐TMSBz‐LSD), in tablet or paper sheet products available online in Japan

Drug Testing and Analysis February 18, 2026 Rie Tanaka, Maiko Kawamura, Michiho Ito et al.

Two new lysergic acid diethylamide (LSD) analogs, 1Bz-LSD and 1-TMSBz-LSD, were identified in tablet and paper sheet products sold in Japan. Using gas chromatography-mass spectrometry, liquid chromatography-photodiode array-mass spectrometry, liquid chromatography with hybrid quadrupole time-of-flight mass spectrometry, and nuclear magnetic resonance, the structures of the compounds were determined. 1Bz-LSD was found in a tablet product, and 1-TMSBz-LSD was found in a paper sheet product. This is the first report of these specific analogs being detected in such products in Japan.

In Vitro Metabolism of 1‐Benzoyl‐Lysergic Acid Diethylamide (1Bz‐LSD) and Identification of a Deethylated Metabolite (1Bz‐LAE) Using a Synthesized Reference Standard

Drug Testing and Analysis February 17, 2026 Yuki Azuma, Akiko Asada, Misa Tanaka et al.

A newly emerged LSD analog, 1-benzoyl-LSD (1Bz-LSD), is rapidly metabolized in human liver microsomes, producing 15 metabolites including LSD itself. One deethylated metabolite remains detectable for a prolonged period, making it a promising target for confirming consumption. This metabolite was chemically synthesized and identified as 1-benzoyl-lysergic acid ethylamide (1Bz-LAE). The synthesis provides a crucial analytical foundation for investigating 1Bz-LSD use, with 1Bz-LAE expected to serve as a valuable marker for detection.