Forensic Science International
October 23, 2020
Anna Åstrand, Davide Guerrieri, Svante Vikingsson et al.
21 citations
Sixty new psychoactive substances (NPS) and their metabolites, including opioids, cannabinoids, and serotonergic hallucinogens, were screened for their ability to activate μ-opioid, CB1, 5-HT1A, and 5-HT2A receptors. Most substances activated their intended target receptor. Among μ-opioid agonists, 2-fluorofentanyl (EC50 = 1.0 nM), carfentanil (EC50 = 2.7 nM), and acrylfentanyl (EC50 = 2.8 nM) were the most potent, with a >1500-fold potency range across compounds. Furanylfentanyl, 4-methoxybutyrylfentanyl, and valerylfentanyl acted as partial agonists. On the 5-HT2A receptor, bromo-dragonfly was the most potent (EC50 = 0.05 nM, 400 times more potent than LSD), followed by NBOMe compounds (EC50 0.11–1.3 nM). Off-target μ-opioid activation occurred for piperazines, phenethylamines, and tryptamines. The synthetic cannabinoid metabolite 3-carboxy indole PB-22 activated 5-HT2A. Bromo-dragonfly activated all four receptors. These findings highlight complex, often overlapping targets among NPS.
Forensic Science International
September 1, 2016
Thomas Gicquel, Chloé Hugbart, Françoise Le Devehat et al.
20 citations
A 30-year-old woman died after consuming a powder she bought online that was labeled as iboga (Tabernanthe iboga). Analysis of the powder found no ibogaine but instead contained toxic alkaloids—ajmaline, yohimbine, and reserpine—which are characteristic of Rauvolfia plant species. Blood concentrations were 109.1 ng/mL ajmaline, 98.2 ng/mL yohimbine, and 30.8 ng/mL reserpine; bile concentrations were much higher. The death was attributed to ingesting a substantial quantity of crushed Rauvolfia roots combined with concomitant drug withdrawal.
Forensic Science International
December 1, 2021
J M Matey, Gemma Montalvo, Carmen García-ruiz et al.
19 citations
Among people who test positive for ketamine, polyconsumption of other drugs and new psychoactive substances (NPS) is common. Reanalyzing hair samples from ten former cases—all defendants accused of crimes against public health—using high-resolution mass spectrometry (UHPLC-HRMS/MS) with a methanolic incubation extraction detected additional NPS not found in the original gas chromatography-mass spectrometry (GC-MS) analysis. The additional substances included other arylcyclohexylamines (deschloroketamine, 3-MeO-PCP, methoxetamine) and cathinones (methylmetcathinone, N-ethyl-pentylone). The new method demonstrated its benefits for NPS prevalence studies.
Forensic Science International
April 1, 2015
Rafael Hernández-bello, Rosa Virginia García-rodríguez, Karlina García-sosa et al.
19 citations
Salvia divinorum products sold as legal highs in Mexico vary widely in their content of the hallucinogenic compound salvinorin A, and declared potencies often do not match measured amounts. Using an HPLC method, concentrations ranged from 8.32 to 56.52 mg/g dried leaf across brands. One brand showed no agreement between its declared and actual salvinorin A content. The emergence of high-strength products (100×), lack of regulation, and this variability could pose health risks to consumers, especially given the potential for psychosis.
Forensic Science International
April 20, 2021
Mengxi Liu, Huan Yang, Jing Hu et al.
14 citations
A fast and reliable UPLC-MS/MS method was developed and validated for measuring dimethyltryptamine (DMT) in hair samples. The method, which pulverizes 20-milligram hair samples with methanol below 4 °C, achieved a lower limit of quantitation of 3 pg/mg and a calibration curve with R² = 0.992. Intraday and interday precision (RSD < 15%) and accuracy (92-113%) were acceptable, and dilution integrity was confirmed. Applied to 28 forensic cases, DMT concentrations ranged from 3 to 1109 pg/mg.
Forensic Science International
April 17, 2020
Sarah Eller, Gabriela Ramos Borges, Daniela Souza Ossanes et al.
13 citations
A new ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed to measure ayahuasca alkaloids in seized herbal products. The method reliably quantifies N,N-dimethyltryptamine (DMT), harmine, harmaline, and tetrahydroharmine, with detection limits of 10 ng/mL for DMT and 25 ng/mL for the β-carbolines. Analysis of four seized samples found DMT concentrations ranging from 31.5 to 46.5 mg/g, but no β-carbolines were detected. The variability in DMT content may help explain potential intoxication cases reported in the literature. The workflow is simple, rapid, and suitable for estimating psychoactive compound levels in forensic materials.
Forensic Science International
July 4, 2018
Pia Simona Bruni, Katharina Elisabeth Grafinger, Susanne Nussbaumer et al.
13 citations
4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET), a new psychoactive substance structurally similar to serotonin, is a serotonergic hallucinogen. To enable forensic urine analysis, its biotransformation was studied using pooled human liver microsomes and three authentic urine samples. Twelve different in vitro and four in vivo metabolites were identified. In vitro, major biotransformation steps included mono- or dihydroxylation, demethylation, demethylation with monohydroxylation, carboxylic acid formation, deethylation, and oxidative deamination. In vivo, monohydroxylation and glucuronidation were observed. A metabolic pathway was proposed. For forensic urine analysis, the N-oxide metabolite, HO-alkyl metabolite, glucuronides of 4-HO-MET, and the parent compound are recommended as target compounds.
Forensic Science International
September 1, 2014
Fernando Xavier Moreira, Félix Carvalho, Maria de Lourdes Bastos et al.
13 citations
Products containing the hallucinogenic plant Salvia divinorum, sold legally in smartshops and online, often mislead consumers about their potency and composition. Analysis of 10 such products, labeled with potencies from 5x to 60x, found that salvinorin A was the primary hallucinogen, along with three related compounds. Labeled concentrations of salvinorin A frequently did not match the actual amounts, and the true concentrations far exceeded the level needed to produce hallucinogenic effects. Safety information was often omitted, encouraging recreational use without adequate warnings.
Forensic Science International
December 1, 2022
Luiz Ferreira Neves Junior, André Luis Fabris, Ingrid Lopes Barbosa et al.
10 citations
LSD prodrugs are emerging as new psychoactive substances in Brazil. Nine blotter paper samples seized by police in São Paulo State were analyzed using gas chromatography-mass spectrometry, infrared spectroscopy, and liquid chromatography-mass spectrometry. The compound was identified as ALD-52 (1A-LSD), an LSD prodrug not controlled by Brazilian legislation, with no other active substances detected. These findings indicate a rising strategy in the designer drug market that warrants attention.
Forensic Science International
April 1, 2022
R Goncalves, N Castaing, C Richeval et al.
10 citations
Methoxpropamine (MXPr), a dissociative drug similar to ketamine, was identified for the first time in France in urine, hair, and powder samples using nuclear magnetic resonance, infrared spectroscopy, and liquid chromatography high-resolution mass spectrometry. In vitro experiments with pooled human liver microsomes and in silico predictions revealed three metabolites: N-despropyl(nor)MXPr, O-desmethyl MXPr, and dihydroMXPr. These metabolites were also detected in urine and hair from a consumer. The work highlights the challenge of identifying new psychoactive substances when they are absent from compound libraries and demonstrates that combining complementary analytical methods with high-resolution mass spectrometry is a promising approach for their molecular characterization.
Forensic Science International
July 4, 2008
Simon D. Brandt, Cláudia P.B. Martins, Sally Freeman et al.
10 citations
DMT, a psychoactive compound, reacts with common laboratory solvents like dichloromethane (DCM) to form a quaternary ammonium salt, which can rearrange during analysis into products including 3-(2-chloroethyl)indole and 2-methyltetrahydro-beta-carboline. This study extends these findings to other halogenated solvents—dibromomethane and 1,2-dichloroethane—characterizing the resulting derivatives. The DCE derivative produced at least six rearrangement products. Using deuterated compounds helped clarify the rearrangement mechanisms. These solvent-derived marker molecules could help identify which solvents were used in the manufacture of controlled substances, a factor often overlooked because solvents are assumed inert.
Forensic Science International
July 1, 2020
Ana Flávia Belchior de Andrade, Mathieu Elie, Christian Weck et al.
8 citations
The drug 25I-NBOH, a new psychoactive substance (NPS), breaks down in the hot injector of a gas chromatograph-mass spectrometer (GC-MS), a common forensic tool, creating misleading byproducts. The main breakdown product is 2C-I, with a smaller amount of an ortho-phenolic benzyl ether (o-PBE) whose exact form depends on the solvent used. Adjusting the injector temperature, split ratio, or flow rate did not prevent this thermal degradation. Thermal analysis showed that 25I-NBOH has a narrow temperature range between melting and decomposing, making it unstable. Derivatization successfully prevented the degradation, allowing accurate GC-MS analysis.
Forensic Science International
November 1, 2024
Julian Bickel, Alexander Müller, Hilke Jungen et al.
3 citations
MDMA (Ecstasy) consumption causes fewer lethal intoxications than opioids despite widespread use. Analysis of post mortem blood samples from eleven MDMA-related fatalities showed wide ranges of MDMA and MDA concentrations and enantiomer ratios. Variability in R/S MDMA ratios could be linked to the time period of metabolism. Hair analysis revealed high MDMA concentrations in all segments regardless of prior drug abuse history, indicating hair analysis may not be suitable for assessing past drug use in ecstasy-related fatalities. Elevated levels of the MDMA enantiomer correlated with longer survival times in intoxication cases, but there was no clear evidence that slowed MDMA metabolism caused lethal intoxications.
Forensic Science International
August 1, 2024
Wing-Chi Cheng, Kwok-Leung Dao, Wing-Cheong Wong
3 citations
Since November 2018, the ketamine analog fluorodeschloroketamine (FDCK) has appeared in Hong Kong forensic cases. A retrospective study of drug seizures and driving-under-the-influence cases up to December 2019 found 74 drug seizure cases (151 items) and 6 drug driving cases. Most seized items contained only FDCK (about 67%) or a mixture with ketamine (about 28%), with purity similar to ketamine seizures. In drug driving cases, blood FDCK concentrations ranged from below 0.002 to 1.1 μg/mL, and other psychoactive substances were also present. The two cases with highest FDCK blood levels (1.1 and 0.87 μg/mL) may have contributed to impairment, though other drugs complicate interpretation.
Forensic Science International
December 16, 2021
Magdalene Huen-Yin Tang, Hok-Fung Tong, Ka-Chung Wong et al.
3 citations
A metabolite of the medication ropinirole (N-despropyl-ropinirole) can cause a false positive for the new psychoactive substance 4-HO-MET in urine drug screening by liquid chromatography tandem mass spectrometry (LC-MS/MS), a method usually considered highly reliable. The interference occurred because the two compounds share similar chemical structures, which fooled standard computer-aided spectral library matching. Careful manual review of mass spectra and comparison with a reference specimen correctly identified the compound. The finding underscores that scientists and pathologists must consider clinical context and drug history when interpreting toxicology results, and that mass spectra should be checked for relative ion ratios when results are questionable. Understanding drug metabolism is essential for troubleshooting such errors.
Forensic Science International
September 1, 1996
Nadia Fucci, Marcello Chiarotti
3 citations
Mescaline was effectively identified using advanced analytical methods, including gas chromatography–mass spectrometry, in a study involving 150 samples. The results showed a 95% accuracy rate in identifying this hallucinogen, highlighting the method's reliability. Additionally, the research demonstrated that these techniques could be applied to assess pharmacokinetics and efficacy of antibiotics, showcasing their versatility in both medicine and analytical chemistry. This approach not only aids in drug identification but also enhances our understanding of pharmacological interactions and biological effects.
Forensic Science International
May 31, 2025
Paweł Stelmaszczyk, Ewa Markiel, Karolina Sekuła et al.
2 citations
A portable sensor system using screen-printed carbon electrodes and square wave voltammetry detects MDMA (ecstasy) in seized drugs. The method achieves a detection limit of 0.5 µM and a linear range of 2.5–50 µM, with high reproducibility, satisfactory precision (intra-day CV%: 2.1–7.1%; inter-day CV%: 5.4–6.3%), and excellent recovery rates (89–105%). Testing on authentic ecstasy samples gave results consistent with a reference UHPLC-DAD method. The system's manual fabrication, low cost, simplicity, and portability suggest strong potential for on-site forensic MDMA detection, even in resource-limited settings.
Forensic Science International
July 1, 2023
Karissa N Resnik, Kala N Babb, Lori W Bekenstein et al.
2 citations
Two white powders bought online as bucinnazine were analyzed by microscopy, DART-MS, and GC-MS. Neither powder contained bucinnazine: powder #1 was 78.0% pure 2-fluoro-deschloroketamine, and powder #2 was 88.9% pure AP-238. The findings raise public health and safety concerns because internet-purchased novel synthetic opioids may contain different active compounds than labeled, and their toxicological risks remain poorly understood.
Forensic Science International
June 1, 2025
A Y Simão, P Y Tokuyama, G Zampieri et al.
1 citation
Analysis of over 900 hair samples from drug users in São Paulo and Rio Grande do Sul, Brazil, found that 29.8% tested positive for at least one drug. Cocaine and its metabolites were most common, with benzoylecgonine in 111 cases, cocaine in 88, and cocaethylene in 37. Cannabinoids were also frequent, including THC in 57 cases and CBN in 48. Adulterants like phenacetin (76 cases), levamisole (14), and strychnine (3) were detected, along with the synthetic cannabinoid 5F-MDMB-PINACA (5 cases) and ketamine (9). Poly-drug use was prevalent, often combining THC with cocaine or benzoylecgonine. The findings illustrate the evolving drug landscape in Brazil and the utility of hair analysis for monitoring drug use.
Forensic Science International
March 1, 2023
Jiaming Zheng, Xin Wang, Jiali Zhang et al.
1 citation
A new LC-MS/MS method was developed to simultaneously extract LSD, iso-LSD, 2-oxo-3-hydroxy-LSD, and 1-propionyl-LSD from hair samples. The method was applied to hair from 18 suspected LSD users. Segmental hair analysis showed LSD concentrations decreasing from the proximal to the distal end, while 1 P-LSD was not detected in any hair segments. The authors report concentrations of LSD and iso-LSD in human hair from 18 LSD users, but note that interpreting hair analysis results for LSD remains difficult.
Forensic Science International
January 1, 2026
Isabella Ferreira Melo, Leociley Rocha Alencar Menezes, Philippe Rodrigues Benedetti et al.
Between 2014 and 2024, forensic analysis of 4911 seized synthetic drug samples (1656 blotter papers and 3255 ecstasy tablets) from Paraná, Brazil, identified 64 distinct chemical substances, 50 of which were new psychoactive substances (NPS). The most common compounds were central nervous system stimulants, particularly phenethylamines. In ecstasy tablets, MDA predominated, while blotter papers most often contained NBOH series compounds. LSD identifications in blotters progressively increased, whereas NPS identifications decreased over time. Most seizures occurred in the state capital, Curitiba, with fewer in border regions. The chemical profile proved diverse and resilient, and the decline in NPS coincided with stricter national and international legislative controls.
Forensic Science International
November 10, 2025
Seonghoon Yeon, Jisu Park, Byungseok Cho et al.
A new fluorinated ketamine analog, 2-fluoro-2-oxo-PCPr, was identified in a 2025 drug seizure. Its chemical structure was determined using NMR, GC-MS, and LC-QTOF-MS. Duplicated NMR signals revealed two interconverting rotameric forms in an approximately 2:1 equilibrium, confirmed by GIAO-based DFT calculations. Metabolite profiling of abusers' urine identified pathways including glucuronidation, desaturation, hydrogenation, hydroxylation, carboxylation, and N-depropylation. The primary metabolite, nor-2-fluoro-2-oxo-PCPr, was detected in both urine and hair, suggesting it may serve as a long-term biomarker. These findings provide key data for detecting and monitoring this emerging psychoactive substance in forensic and clinical toxicology.
Forensic Science International
September 1, 2026
Byungsuk Cho, Seonghoon Yeon, Sanghee Woo et al.
A white powder submitted to South Korea's National Forensic Service in early 2025 was identified as 2F-2-oxo-PCPr, a new ketamine analogue with fluorine replacing chlorine and a propyl group replacing the amine methyl group. Because ketamine produces hallucinogenic and dissociative effects by blocking NMDA receptors, this analogue may act similarly. To detect such substances in biological samples, researchers developed and validated a liquid chromatography-tandem mass spectrometry method for simultaneously measuring 2F-2-oxo-PCPr, 2F-2-oxo-PCE, 2F-deschloroketamine, ketamine, and their metabolites in human hair. The method met all validation criteria and was applied to hair from eight individuals suspected of using ketamine-related drugs. This is the first reported single hair-based workflow covering ketamine alongside three fluorinated analogues and their metabolites.
Forensic Science International
May 7, 2020
M. H. Tang, Terence C. Li, C. Lai et al.
A new ketamine-like drug called 2-fluorodeschloroketamine (2F-DCK) has been identified in patients, often alongside other similar substances. Between January and July 2019, 20 cases of confirmed 2F-DCK exposure were reported, with 19 involving at least one other ketamine-type drug, most commonly ketamine (90%), deschloroketamine (50%), and 2-oxo-PCE (45%). Six patients had four different ketamine-type drugs in their urine. Clinical effects were primarily neurological (impaired consciousness, agitation, abnormal behavior) and cardiovascular (hypertension, tachycardia); five patients experienced loss of consciousness or convulsions. All patients recovered with supportive care. This is the first clinical case series of 2F-DCK, highlighting the need for awareness of this expanding class of drugs and frequent co-ingestion of multiple analogues.
Forensic Science International
November 1, 2019
Roujia Wang, Ping Xiang, Zhiguo Yu et al.
A new method using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed to measure the designer hallucinogen 5-MeO-DiPT in human hair. The method was validated and applied to 106 real cases of suspected users, finding hair concentrations ranging from 0.2 to 7532.5 pg/mg. The technique provides a way to document illegal use of this synthetic tryptamine derivative.