Journal of Pharmaceutical and Biomedical Analysis
August 26, 2002
Felix Hasler, Daniel Bourquin, Rudolf Brenneisen et al.
100 citations
After oral doses of psilocybin (212 ± 25 µg/kg body weight), the metabolite psilocin appears in urine, peaking at 870 µg/L between 2 and 4 hours. Within 24 hours, 3.4 ± 0.9% of the dose is excreted as free psilocin. Adding beta-glucuronidase doubles measured psilocin levels, indicating partial excretion as psilocin-O-glucuronide, though 18 ± 7% of unconjugated psilocin decomposes during incubation. Enzymatic hydrolysis extends detectability in urine.
Journal of Pharmaceutical and Biomedical Analysis
June 9, 2008
Simona Pichini, Mitona Pujadas, Emilia Marchei et al.
59 citations
A liquid chromatography-mass spectrometry (LC-MS) method was developed to measure ten designer drugs—including MDMA, several 2C-series phenethylamines, m-CPP, and tryptamines—in urine samples from 32 consumers. Solid-phase extraction at pH 6 was applied to both non-hydrolyzed and enzymatically hydrolyzed urine, with 3,4-methylendioxypropylamphetamine (MDPA) as an internal standard. Chromatographic separation used a C18 column with a gradient of ammonium bicarbonate and acetonitrile, and detection was performed in single ion monitoring mode with electrospray ionization. Limits of quantification ranged from 20 to 60 ng/mL, calibration curves were linear to 2000 ng/mL, and mean recoveries were 55.4–95.6%. Higher analyte concentrations in hydrolyzed samples indicated the presence of conjugated compounds.
Journal of Pharmaceutical and Biomedical Analysis
February 5, 2020
Alfredo Fabrizio Lo Faro, Annagiulia Di Trana, Nunzia La Maida et al.
45 citations
New psychoactive substances of natural origin, mainly alkaloids from Asian and South American plants, typically have stimulant or hallucinogenic effects, with a few having sedative properties. Information on analytical identification of these substances in plant material is scarce, and there is little data on their characterization and quantification in biological matrices from intoxication or fatality cases. Their metabolism is not fully investigated, making identification infrequent and metabolites often unknown.
Journal of Pharmaceutical and Biomedical Analysis
November 1, 2014
Simona Pichini, Emilia Marchei, Oscar García-algar et al.
44 citations
A new laboratory method using ultra-high-pressure liquid chromatography tandem mass spectrometry can detect and measure mescaline, N,N-dimethyltryptamine, psilocin, psilocybin, and salvinorin A in hair from people who use psychedelic plants such as peyote, trichocereus cacti, psilocybe mushrooms, Salvia divinorum, or the beverage ayahuasca. The method is accurate and precise, with detection limits as low as 0.03–0.05 nanograms per milligram of hair. Testing on actual users found mescaline at 0.08–0.13 ng/mg in peyote smokers, 3.2 ng/mg salvinorin A in a Salvia divinorum smoker, 5.6 ng/mg N,N-dimethyltryptamine in an ayahuasca user, and 0.8 ng/mg psilocybin in a psilocybe consumer.
Journal of Pharmaceutical and Biomedical Analysis
November 27, 2016
Achim T. Caspar, Simon D. Brandt, Andreas E. Stoever et al.
43 citations
25B-NBOMe and 25C-NBOMe, potent 5-HT2A receptor agonists linked to hallucinogenic effects and severe intoxications, are extensively metabolized in rats and humans. Using LC-HR-MS/MS, 66 metabolites were identified for 25B-NBOMe and 69 for 25C-NBOMe, primarily through O-demethylation, O,O-bis-demethylation, hydroxylation, and subsequent glucuronidation and sulfation. After low-dose administration to rats, both substances were detectable mainly via their metabolites using LC-based screening approaches. In an authentic human urine sample from an acute intoxication, 25B-NBOMe and its metabolites were detected by GC-MS as well. Initial screening showed CYP1A2 and CYP3A4 involvement in hydroxylation, and CYP2C9 and CYP2C19 in O-demethylation.
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.
Journal of Pharmaceutical and Biomedical Analysis
August 1, 2022
Jan Thomann, Laura Ley, Aaron Klaiber et al.
23 citations
A bioanalytical method using ultra-high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and validated to rapidly quantify mescaline and its metabolites (TMPAA, NAM, and 4-desmethyl mescaline) in human plasma. The single-step protein precipitation extraction achieved complete recovery (≥98.3%) with minor matrix effects (≤7.58%). Intra-assay accuracy ranged from 84.9% to 106%, and precision was ≤7.33%. The method's sensitivity allowed lower limits of quantification of 12.5 ng/mL for mescaline and TMPAA, and 1.25 ng/mL for NAM, sufficient for clinical pharmacokinetic studies. However, 4-desmethyl mescaline could not be selectively quantified due to interference from another metabolite. The method is reliable and easy-to-use for forensic and clinical pharmacokinetic applications.
Journal of Pharmaceutical and Biomedical Analysis
June 15, 2024
Rossella Barone, Guido Pelletti, Arianna Giorgetti et al.
22 citations
A new method using ultra-high performance liquid chromatography mass spectrometry can detect and quantify 122 new psychoactive substances (NPS) and 15 classical drugs of abuse (DoA) in hair samples. The method was validated according to European Medicines Agency guidelines and applied to 22 authentic forensic hair samples. Among these, 17 tested positive for DoA and 10 for NPS, with most samples showing co-occurrence of both. Detected NPS included ketamine, norketamine, 5-MMPA, ritalinic acid, methoxyacetyl fentanyl, methylone, and RCS-4. The approach offers a cost-effective, wide-panel tool for forensic laboratories to assess NPS prevalence and co-use with classical drugs.
Journal of Pharmaceutical and Biomedical Analysis
July 21, 2020
Izumi Morita, Hiroyuki Oyama, Yuki Kiguchi et al.
17 citations
Two independent monoclonal antibodies were generated against psilocybin and its dephosphorylated metabolite psilocin, the psychoactive compounds in hallucinogenic mushrooms. Novel immunogenic conjugates were prepared by modifying the side chains of these molecules and linking them to carrier proteins. Mice were immunized, and hybridoma clones secreting the specific antibodies were established. Competitive enzyme-linked immunosorbent assays (ELISAs) using these antibodies enabled detection of psilocybin and psilocin at ranges of approximately 0.20–20 μg/assay and 0.040–2.0 μg/assay, respectively, with low cross-reactivity between the two compounds. In dried Psilocybe cubensis powder, psilocybin and psilocin contents were 0.39% and 0.32% by weight. These ELISAs offer a promising tool for identifying illegal hallucinogenic mushrooms.
Journal of Pharmaceutical and Biomedical Analysis
March 23, 2016
Veniero Gambaro, Gabriella Roda, Giacomo Luca Visconti et al.
17 citations
DNA-based identification of biological material in hallucinogenic mushroom culture media enables forensic identification of illegal samples even when only basidiospores are present, without needing fruiting bodies. This approach allows customs to stop and destroy potentially illicit material before cultivation, avoiding the need for criminal cases. A validated LC-UV method with a cation exchange column quantified psilocybin and psilocin in mushrooms grown from seized grow-kits. Psilocybin content ranged from 1.02 to 7.60 mg/g of dry material, and psilocin from 0.415 to 8.36 mg/g. The method showed linearity (R² > 0.9992), low detection limits, and high precision.
Journal of Pharmaceutical and Biomedical Analysis
September 9, 2020
Tímea Körmöczi, Írisz Szabó, Eszter Farkas et al.
15 citations
A new two-dimensional liquid chromatography method coupled to high-resolution tandem mass spectrometry was developed to measure the level of N,N-dimethyltriptamine (DMT) in rat plasma and brain tissue. The method achieved high recovery (90% in plasma, 88% in brain) and sensitivity (limit of detection 0.108 ng/mL in plasma, 0.212 ng/g in brain) within a 10-minute run. In an experimental model of cerebral ischemia/reperfusion, DMT concentration in rat plasma before hypoxia (49.3–114.3 ng/mL) was generally higher than after hypoxia (10.6–96.1 ng/mL). After treatment, brain DMT levels rose to 2–6.1 ng/g. The approach reliably detects and confirms DMT administered therapeutically.
Journal of Pharmaceutical and Biomedical Analysis
January 20, 2024
Alfredo Fabrizio Lo Faro, Giorgia Sprega, Diletta Beradinelli et al.
14 citations
Enantioselective high-performance liquid chromatography-tandem mass spectrometry methods were developed to quantify MDMA and its phase-1 metabolites HMA, HMMA, and MDA in human plasma, sweat, oral fluid, and urine. Two polysaccharide-based chiral columns achieved baseline separation of most enantiomer pairs: the Lux AMP column separated MDMA, HMA, and HMMA enantiomers but not MDA; the Lux i-Amylose-3 column separated MDMA, HMMA, and MDA enantiomers but not HMA. Analysis took under 4 minutes with one column and under 6 minutes with the other. Both methods were validated and applied to biological fluids, confirming enantioselective metabolism of MDMA.
Journal of Pharmaceutical and Biomedical Analysis
September 20, 2023
Ziyi Li, Zehong Li, Wanting Xie et al.
13 citations
A method using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated to detect phencyclidine-type substances in human hair. The method showed good sensitivity, selectivity, and accuracy. It was applied to hair samples from 87 authentic forensic cases, identifying and quantifying nine analytes including ketamine, 2-F-2-oxo-PCE, 2-FDCK, 2-BrDCK, nor2-FDCK, tiletamine, O-PCE, DCK, and norDCK at various concentrations. This approach provides technical support for monitoring abuse of these substances, which are often synthesized as substitutes for controlled drugs.
Journal of Pharmaceutical and Biomedical Analysis
August 1, 2024
Tanja M Gampfer, Victoria Schütz, Philip Schippers et al.
11 citations
Two new hallucinogenic drugs, 1cP-LSD and 4-AcO-DET, were metabolized in human liver S9 fraction and in zebrafish larvae, with several phase I and phase II metabolites identified. Some metabolites were unique to zebrafish larvae. Neither compound showed toxic effects on human liver cells, though 4-AcO-DET combined with a CYP inhibitor altered two cellular parameters at concentrations far above expected in vivo levels. The authors suggest further testing with other liver cell lines that express more CYP enzymes.
Journal of Pharmaceutical and Biomedical Analysis
December 28, 2007
Simon D. Brandt, Cláudia P.B. Martins, Sally Freeman et al.
10 citations
DMT, a simple tryptamine with powerful psychoactive properties, reacts with dichloromethane during work-up or long-term storage, forming the quaternary ammonium salt N-chloromethyl-DMT chloride. Analysis of this side-product by gas chromatography ion trap mass spectrometry (GC-MS) yielded only degradation products, such as 3-(2-chloroethyl)indole and 2-methyltetrahydro-beta-carboline, while HPLC detected the original salt. Because GC-MS is standard for drug fingerprinting, the presence of these degradation products could lead to erroneous conclusions about the synthetic route of a DMT sample.
Journal of Pharmaceutical and Biomedical Analysis
July 15, 2024
Ettore Ferrari Júnior, Victor Souza Bitencourt, Ágatha Beatriz Mariano de Souza et al.
9 citations
A validated method using a modified QuEChERS extraction and liquid chromatography-tandem mass spectrometry can detect 51 psychoactive substances and screen for 22 more in oral fluid from electronic dance music party attendees. Storage at -20°C without buffer preserved substances for up to 72 hours with less than 15% loss. Analysis of 62 real samples found MDMA and MDA in 27 samples (concentrations up to 829 ng/mL), cocaine and metabolites in 8 samples, and methamphetamine in 8 samples. Eutylone was detected in two cases where attendees reported taking 'ecstasy.' Comparison with self-reports showed that illicit drug use is often underreported and attendees are frequently unaware of what they consume.
Journal of Pharmaceutical and Biomedical Analysis
July 15, 2022
Graeme Cochrane, Jennifer K Field, Matthew C Hulme et al.
9 citations
Supercritical fluid chromatography (SFC) with a carbon dioxide and ammonium acetate gradient separates 31 novel diphenidine-derived psychoactive substances, including regioisomers, in under 10 minutes. Different stationary phases (acidic, neutral, basic) produce medium to large selectivity differences between isomers. Acidic silica phases retain diphenidines longer via electrostatic attraction, while basic phases reduce retention via repulsion. Baseline separation is achieved for six of eight substituted groups on a simple silica column. As halo-substituent size increases, resolution between ortho- and meta-isomers decreases, causing co-elution of ortho- and meta-bromodiphenidines. Elution orders differ from reversed-phase UHPLC, providing orthogonal separation, with hydrophilic compounds better retained on SFC columns.
Journal of Pharmaceutical and Biomedical Analysis
June 15, 2024
Romain Magny, Bruno Mégarbane, Lucie Chevillard et al.
7 citations
A chronic user of GHB, 3-MMC, and methoxetamine lost consciousness during a chemsex session and was admitted to intensive care, recovering quickly. Analysis of ten plasma samples over 29.5 hours, plus urine, hair, and a seized crystal, using liquid and gas chromatography, mass spectrometry, and nuclear magnetic resonance, confirmed exposure to multiple drugs including GHB, two benzofurans, two cathinones, and a new psychoactive substance: deschloro-N-ethyl-ketamine (O-PCE), an arylcyclohexylamine. Molecular networking identified 27 O-PCE metabolites, some previously unreported. O-PCE had an elimination half-life of about 5 hours. Lipid metabolism was markedly altered, likely from polydrug use.
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.
Journal of Pharmaceutical and Biomedical Analysis
June 15, 2024
Giorgia Sprega, Giorgi Kobidze, Alfredo Fabrizio Lo Faro et al.
4 citations
An improved chiral LC-MS/MS method separates all four pairs of enantiomers of MDMA and its major phase-1 metabolites (HMA, HMMA, MDA) on a single Lux AMP column within six minutes, using an optimized mobile phase and column dimensions. The method was applied to human plasma, oral fluid, and urine. In urine, hydrolysis of glucuronides with hydrochloric acid or glucuronidase was tested to evaluate effects on the concentration and enantiomeric distribution of the hydroxy metabolites HMA and HMMA.
Journal of Pharmaceutical and Biomedical Analysis
July 15, 2022
Jennifer K Field, Christine Hinz, Christopher M Titman et al.
4 citations
A rapid UHPLC-MS/MS method can detect and confirm 33 different diphenidine derivatives in solid drug samples. The method separates compounds based on the position and type of chemical substituents on the phenyl ring, and it works even when common adulterants are present. The 10-minute protocol was successfully used to identify psychoactive components in four seized drug samples from law enforcement.
Journal of Pharmaceutical and Biomedical Analysis
October 15, 2025
Zihe Yang, Linjie Li, Bin Deng et al.
3 citations
After intranasal administration in rats, ketamine rapidly enters the bloodstream, reaching a peak concentration of 8002 ng/mL within about 5 minutes, then declines to near zero by about 3 hours, with a half-life of 27 minutes. Tissue analysis shows the highest ketamine levels in the kidneys, followed by the liver. Within the brain, ketamine concentrates most in the hypothalamus and hippocampus, with lower amounts in the striatum and prefrontal cortex. These findings clarify how ketamine distributes throughout the body and brain after intranasal delivery, providing a basis for understanding its clinical use in treating depression.
Journal of Pharmaceutical and Biomedical Analysis
August 1, 2026
Magdaléna Vágnerová, Petr Palivec, Monika Mrňavá et al.
The metabolism of the recreational drug 25E-NBOH was investigated in human liver microsomes, rat urine, and Cunninghamella elegans fungus. Using untargeted LC-HRMS/MS, 56 metabolites were annotated, many as isomers. Primary metabolic pathways included hydroxylation, O-demethylation, and N-debenzylation, followed by conjugation. Ten reference substances were synthesized; seven matched detected metabolites by retention time and MS/MS spectra, enabling structural assignment. The known psychoactive substance 2C-E was confirmed as a metabolite. Three main biomarkers are proposed. This work provides the first comprehensive metabolic profile of 25E-NBOH, supporting future pharmacological and toxicological studies and aiding clinical diagnosis of intoxication.
Journal of Pharmaceutical and Biomedical Analysis
June 24, 2026
Scot Mcintosh, Isabella Maldonado, Nickalus C Smith et al.
A sensitive UPLC-MS/MS method was developed and validated to quantify ibogaine, noribogaine, ibogamine, and oxa-noribogaine in rat brain microdialysate, measuring pharmacologically active, unbound drug in brain extracellular fluid rather than total tissue content. The method achieved lower limits of quantification of 0.78-1.56 ng/mL with a 6-minute run time, and calibration curves were linear over 0.78-75 ng/mL for ibogamine and 1.56-75 ng/mL for the other analytes. Accuracy and precision met acceptance criteria. Applied to rats (n=4), noribogaine in nucleus accumbens after 10 mg/kg intraperitoneal administration reached a peak unbound concentration of 292 ± 68 ng/mL at 50 minutes, demonstrating suitability for real-time neuropharmacokinetic profiling of iboga alkaloids.
Journal of Pharmaceutical and Biomedical Analysis
August 15, 2025
Zhen Zhang, Yan Shi, Meiting Lin et al.
A UHPLC-MS/MS method was developed to separate and measure the two mirror-image forms (enantiomers) of ketamine in human urine and hair. After a deceased person used esketamine before death, only S-ketamine appeared in blood and urine, indicating that ketamine does not switch between its enantiomeric forms in the body. In 45 hair samples from ketamine abusers, the ratio of R-ketamine to S-ketamine ranged from 0.809 to 1.43, showing that illegal-market ketamine is mostly racemic (equal parts both enantiomers). A significant difference in this ratio was found between samples from China and Myanmar, likely due to regional variations in synthetic routes.