JournalTOCs

Forensic Toxicology
Journal Prestige (SJR): 1.407

Citation Impact (citeScore): 3
Number of Followers: 19

Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1860-8973 - ISSN (Online) 1860-8965
Published by Springer-Verlag

[2467 journals]

Acute, chronic, and post-mortem toxicity: a review focused on three
different classes of new psychoactive substances
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  Abstract: Purpose New psychoactive substances (NPS) are not controlled under the Single Convention on Narcotic Drugs of 1961 or the 1971 Convention, but they may pose a public health threat. Knowledge of the main properties and toxicological effects of these substances is lacking. According to the current Drugs Law (Law n. 11.343/2006), the Brazilian Surveillance Agency issues directives for forbidden substances in Brazil, and structural classes of synthetic cannabinoids, cathinones, and phenylethylamines are considered illicit drugs. Considering that data on these controlled substances are scattered, the main objective of this work was to collect and organize data to generate relevant information on the toxicological properties of NPS. Methods We carried out a literature review collecting information on the acute, chronic, and post-mortem toxicity of these classes of NSP. We searched info in five scientific databases considering works from 2017 to 2021 and performed a statistical evaluation of the data. Results Results have shown a general lack of studies in this field given that many NPS have not had their toxicity evaluated. We observed a significant difference in the volume of data concerning acute and chronic/post-mortem toxicity. Moreover, studies on the adverse effects of polydrug use are scarce. Conclusions More in-depth information about the main threats involving NPS use are needed.
  PubDate: 2023-01-06
Urinary profiles of methoxyphenamine and its metabolite after inhalation
of methoxyphenamine smoke in humans: aiming to distinguish between active
and passive exposure
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  Abstract: Purpose Methamphetamine (METH) is commonly abused through smoking. However, the lack of evidence regarding differences in urinary METH excretion after its active and passive inhalation has resulted in complications where the accused claims passive exposure. This study aimed to determine the differences in urinary excretion after active and passive inhalation of the drug, using methoxyphenamine (MPA) as a model for METH. Methods Body temperature and locomotor activity were measured in mice as indicators of central nervous system toxicity. Six healthy adult male subjects were exposed to passive or active inhalation of MPA smoke in a small room, and urine samples were taken. MPA concentrations were measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results There were no signs of toxicity in mice exposed to MPA smoke, ensuring the safety of the clinical study. Urinary MPA concentrations were significantly lower with passive inhalation compared with those of active inhalation. The maximum urinary MPA concentration in passive inhalation was 13.4 ng/mL, which was 1/60 of active inhalation with 800 ng/mL. The urinary excretion in passive inhalation until 24 h was 8.21 μg, which was 1/76 of active inhalation with 625 μg. Conclusions Since METH and MPA are expected to be excreted similarly, urinary METH concentrations in passively exposed persons are expected to be lower than the cutoff value of the screening kit. If the urine screening test is positive, the suspect should be considered a METH user. Trial registration number: jRCTs031210604, registration date: Feb. 9, 2022.
  PubDate: 2023-01-06
Blood transfusion causing false positive PEth
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  PubDate: 2023-01-01
Simultaneous fatal poisoning of two victims with 4F-MDMB-BINACA and
ethanol
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  Abstract: Purpose Methyl-2-(1-(4-fluorobutyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (4F-MDMB-BINACA) is a newly emerging synthetic cannabinoid receptor agonists (SCRA) first described in 2018 in both Europe and the United States. Two fatal cases are reported caused by simultaneous consumption of 4F-MDMB-BINACA and ethanol. Methods The victims were brothers who were both found deceased after consuming 4F-MDMB-BINACA and ethanol. Post-mortem toxicological analyses of blood and urine were carried out by supercritical fluid chromatography tandem mass spectrometry (SFC–MS/MS) and headspace gas chromatography with flame ionization detection (HS-GC–FID). Results The concentration of 4F-MDMB-BINACA in the postmortem blood was 2.50 and 2.34 ng/mL, and blood alcohol concentration was 2.11 and 2.49 g/L, respectively. Conclusion According to the reported cases and reviews of the scientific literature, concurrent ethanol consumption should amplify the toxicity of SCRAs. The threshold SCRA concentration for fatal overdose can be estimated ng/mL level (0.37–4.1 ng/mL according to the reported cases) in cases in which 1.5–2.5 g/L of ethanol is present in the blood.
  PubDate: 2023-01-01
An unusual case of fatal hypothermia involving topical diphenhydramine
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  Abstract: Purpose Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine. Methods A 23-year-old male with no known preexisting medical conditions was found dead in the bathroom of his apartment with a small amount of running water on his back. Postmortem examinations and toxicological analysis on blood and urine were performed. Results Color difference was apparent between the right and left cardiac blood. Wischnewski spots were observed in the gastric mucosa. Histological examination revealed no obvious findings that could attribute to serious cardiovascular events. Drug screening by gas chromatograph-tandem mass spectrometry (GC/MS/MS) detected diphenhydramine in blood and urine. Further quantification revealed the postmortem concentrations to be 0.44 μg/mL in blood and 2500 μg/mL in urine. Conclusions The cause of death was determined to be hypothermia. Diphenhydramine-induced drowsiness and possible intrinsic cardiac factor may have led to prolonged impaired consciousness, preventing his ability to escape from the running cold water leading to hypothermia and death.
  PubDate: 2023-01-01
Analysis of degradation products of nerve agents in biological fluids by
ion chromatography–tandem mass spectrometry
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  Abstract: Purpose The detection of hydrolysis products of nerve agents (alkyl methylphosphonic acids; RMPAs) in biological samples from victims is important to confirm exposure to nerve agents. However, analysis of RMPAs is difficult due to their high hydrophilicity. The aim of this study was to develop ion chromatography–tandem mass spectrometry (IC–MS/MS) methods using commercially available equipment and columns to analyze RMPAs in human urine and serum with high sensitivity and without using complicate techniques. Methods A Dionex IonPac AS11-HC anion-exchange column was used to analyze six RMPAs (MPA, EMPA, IMPA, iBuMPA, CHMPA, and PMPA). For pretreatments of biological fluids, we developed two pretreatment methods (Method 1: dilution and ultrafiltration; Method 2: removal of chloride ions with Ag cartridges). Results Six RMPAs including highly hydrophilic methylphosphonic acid and ethyl methylphosphonic acid could be analyzed with sufficient retention times and peak shape. The detection limits of RMPAs were improved using Dionex OnGuard II Ba/Ag/H cartridges and MetaSEP IC–Ag cartridges (urine: 0.5–5 ng/mL; serum: 1–5 ng/mL). These methods were also applied to the test samples for the Organisation for the Prohibition of Chemical Weapons Biomedical Proficiency Tests. Conclusions RMPAs could be sufficiently analyzed by IC–MS/MS. In addition, the limits of detection were superior to those obtained in our previous study involving LC–MS/MS or derivatization–LC–MS/MS method. For analysis of biological samples, an appropriate pretreatment method can be chosen according to the amount of sample available for analysis and expected RMPA concentrations.
  PubDate: 2023-01-01
Development and validation of an ultra-performance liquid
chromatography–tandem mass spectrometric method for the determination of
25 psychoactive drugs in cerumen and its application to real postmortem
samples
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  Abstract: Purpose In the present study, a method for the detection of 25 psychoactive substances in cerumen was developed and validated. This method targets opiates, cocaine, antidepressants, benzodiazepines, antipsychotics and antiparkinsons. Methods Analysis was performed on a SCIEX Triple Quad 6500+ system after liquid–liquid extraction. Methanol with 1% acetic acid was chosen as the extraction solvent. After the addition of the solvent, samples were vortexed, sonicated, centrifuged and directly injected into the liquid chromatography–tandem mass spectrometry system. Results The method was found to be selective and sensitive (limit of detection: 0.017 ng–0.33 ng/mg), the assay was linear for all analytes with linear regression coefficient ranging 0.9911–1.00. The values for intra-assay precision was between 4.34 and 14.6% and inter-assay precision between 5.81 and 17.7%, with accuracy within the acceptable criteria for all analytes. All analytes in cerumen specimens were stable for 48 h at 4 °C and 72 h at − 20 °C, whilst no significant matrix effect or carryover was observed. Applicability was proven by analyzing cerumen samples from 25 deceased with a history of drug abuse. All analytes were detected in real samples, thus confirming the sensitivity of the developed method. Conclusions According to our knowledge, it is the first time that a method for the simultaneous detection of 25 psychoactive drugs in cerumen was developed, fully validated and finally applied to 25 postmortem samples.
  PubDate: 2023-01-01
Methyl (S)-2-(1–7
(5-fluoropentyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate
(5F-MDMB-PICA) intoxication in a child with identification of two new
metabolites (ultra-high-performance liquid chromatography–tandem mass
spectrometry)
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  Abstract: Purpose Methyl (S)-2-(1–7 (5-fluoropentyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMA-PICA) intoxication in 1.5-year-old child was presented, together with diagnostic parameters discussion and 5F-MDMB-PICA determination in biological material. Furthermore, 5F-MDMB-PICA metabolites were identified in a urine sample as markers of exposure in situation when a parent compound is not present in specimens. Methods Drugs and metabolites were extracted from serum and urine with ethyl acetate both under alkaline (pH 9) and acidic (pH 3) conditions. Hair, after decontamination and pulverization, were incubated with methanol (16 h, 60 °C). The analysis was carried out using ultra-high-performance liquid chromatography–tandem mass spectrometry. For the identification of 5F-MDMB-PICA metabolites, an urine sample was precipitated with cold acetonitrile. Analysis was performed using ultra-high-performance liquid chromatograph with quadrupole time-of-flight mass spectrometer. Results 5F-MDMB-PICA was determined only in serum sample at concentration of 298 ng/mL. After 1 year, when analysis was repeated, concentration of synthetic cannabinoid in the same sample was only 17.6 ng/mL which revealed high instability of 5F-MDMB-PICA in serum sample. Eight 5F-MDMB-PICA metabolites were identified in urine sample, including two potentially new ones with m/z 391.18964 and m/z 275.14016. Conclusions Toxicological analysis confirmed a 1.5-year-old boy intoxication with 5F-MDMB-PICA. Besides the parent drug, metabolites of 5F-MDMB-PICA were identified, including two potentially new ones, together with possible metabolic reactions which they resulted from. Metabolites determination could serve as a marker of 5F-MDMB-PICA exposure when no parent drug is present in biological material.
  PubDate: 2023-01-01
The next addiction-causing drug class 4-quinazolinone derivatives:
analyses of methaqualone analogs including recently discovered
2-methoxyqualone by different modes of mass spectrometry
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  Abstract: Purpose The information on analytical methods for 4-quinazolinone recreational drugs, such as methaqualone, etaqualone and 2-methoxyqualone, is almost scant. In this study, product ion spectra of gas chromatography−tandem mass spectrometry (GC−MS/MS) with different collision energies were presented for these drugs. Because 2-methoxyqualone is a new recreational drug discovered in dubious tablets very recently, much more detailed data obtained by different types of mass spectrometry instruments, and quantification data of 2-methoxyqualone in the tablet together with its validation were demonstrated. Methods The methods for analyses were GC−MS/MS, high-resolution ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry and liquid chromatography−tandem mass spectrometry. Results The GC−MS/MS product ion spectra of the three compounds with different collision energies have not been reported before. They were very useful to tentatively identify unknown compounds. If a reference standard is available, the final identification and quantification can be achieved by measurements of product ion spectra and in selected reaction monitoring mode very easily by GC−MS/MS. The final identification and quantification for the new 2-methoxyqualone were performed in this way. The content of the compound was 69.8 ± 0.5% (w/w) in the tablet. Acetaminophen and caffeine coexisted in the tablet with approximate concentrations at 10 and 5%, respectively. Conclusions In this article, we have presented product ion spectra of methaqualone, etaqualone and 2-methoxyqualone at different collision energies by GC−MS/MS for the first time. In addition, this is the first paper to describe the details of quantification of 2-methoxyqualone in the authentic seized product.
  PubDate: 2023-01-01
Rapid quantification of phenobarbital and barbital in human whole blood by
liquid–liquid extraction combined with DART-orbitrap-HRMS
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  Abstract: Purpose This study aims to develop and validate a rapid, simple, and efficient bioanalytical method for the simultaneous quantification of phenobarbital and barbital in human whole blood using liquid–liquid extraction combined with direct analysis in real time (DART) and high-resolution mass spectrometry (HRMS). Method Phenobarbital-d5 and aprobarbital were selected as internal standards (ISs) of phenobarbital and barbital, respectively. A mixed solvent of o-xylene and ethyl acetate at a ratio of 1:6 was used to extract analytes of interest and ISs from 100 μL of human whole blood samples. Phenobarbital and barbital were detected by DART-HRMS. The proposed method has been validated in accordance with United States Food and Drug Administration Guidelines for Bioanalytical Method Validation in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery, stability, and dilution integrity. Results The lower limits of quantification (LLOQs) of phenobarbital and barbital were both 10 ng/mL. The linearities were in the range of 10–1000 ng/mL (R2 ≥ 0.99). The mean recovery values of phenobarbital and barbital were 99.7% and 88.1%, respectively. The interday and intraday precision values were less than 10.4%, and the interday and intraday accuracy values ranged from 87.6 to 106.7%. Furthermore, the validated method was applied to four cases of phenobarbital poisoning at the Shanghai Institute of Forensic Science. Conclusion The developed and fully validated method enabled the simultaneous quantification of phenobarbital and barbital in human whole blood and was successfully applied to authentic cases.
  PubDate: 2022-11-27
Correction to: A potential of methoxpropamine to be a widespread
recreational drug: it blocks NMDA receptors and inhibits NMDA
receptor-mediated synaptic transmission in a brain preparation of mice
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  PubDate: 2022-11-09
  DOI: 10.1007/s11419-022-00651-9
Characterisation of AMB-FUBINACA metabolism and CB1-mediated activity of
its acid metabolite
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  Abstract: Purpose AMB-FUBINACA is a synthetic cannabinoid receptor agonist (SCRA) which is primarily metabolised by hepatic enzymes producing AMB-FUBINACA carboxylic acid. The metabolising enzymes associated with this biotransformation remain unknown. This study aimed to determine if AMB-FUBINACA metabolism could be reduced in the presence of carboxylesterase (CES) inhibitors and recreational drugs commonly consumed with it. The affinity and activity of the AMB-FUBINACA acid metabolite at the cannabinoid type-1 receptor (CB1) was investigated to determine the activity of the metabolite. Methods The effect of CES1 and CES2 inhibitors, and delta-9-tetrahydrocannabinol (Δ9-THC) on AMB-FUBINACA metabolism were determined using both human liver microsomes (HLM) and recombinant carboxylesterases. Radioligand binding and cAMP assays comparing AMB-FUBINACA and AMB-FUBINACA acid were carried out in HEK293 cells expressing human CB1. Results AMB-FUBINACA was rapidly metabolised by HLM in the presence and absence of NADPH. Additionally, CES1 and CES2 inhibitors both significantly reduced AMB-FUBINACA metabolism. Furthermore, digitonin (100 µM) significantly inhibited CES1-mediated metabolism of AMB-FUBINACA by ~ 56%, while the effects elicited by Δ9-THC were not statistically significant. AMB-FUBINACA acid produced only 26% radioligand displacement consistent with low affinity binding. In cAMP assays, the potency of AMB-FUBINACA was ~ 3000-fold greater at CB1 as compared to the acid metabolite. Conclusions CES1A1 was identified as the main hepatic enzyme responsible for the metabolism of AMB-FUBINACA to its less potent carboxylic acid metabolite. This biotransformation was significantly inhibited by digitonin. Since other xenobiotics may also inhibit similar SCRA metabolic pathways, understanding these interactions may elucidate why some users experience high levels of harm following SCRA use.
  PubDate: 2022-10-28
  DOI: 10.1007/s11419-022-00649-3
Correction to: A chasing dead-end case report: a fatal lead intoxication
following an attempted homicide
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  PubDate: 2022-10-14
  DOI: 10.1007/s11419-022-00647-5
Correction to: Difficulties interpreting concentrations in fatal cases:
example of 2,5-dimethoxy-4-chloroamphetamine
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  PubDate: 2022-10-12
  DOI: 10.1007/s11419-022-00648-4
The mystery behind the apprehensions of the selective cannabinoid receptor
type-2 agonist BZO-HEXOXIZID (MDA-19) as a drug of abuse
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  Abstract: Purpose MDA-19 or BZO-HEXOXIZID (N′-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-benzohydrazide), in a more recent nomenclature, was first synthesized in 2008 as a selective type-2 cannabinoid receptor (CB2) agonist due to its potential to treat neuropathic pain. In Brazil, this substance was identified in a series of 53 apprehensions between September 2021 and February 2022. Nevertheless, what intrigues toxicologists is that BZO-HEXOXIZID does not exert significant type-1 cannabinoid receptor (CB1) agonism—which is responsible for the well-known psychoactivity of Δ-9-tetrahydrocannabinol. Thus, the objective of this work is to report the first apprehension and identification of BZO-HEXOXIZID in Brazil and to discuss pharmacologically the possible reasons why a CB2 agonist has been incorporated to the illicit market. Methods Suspected seized samples were sent to the Laboratory of the Scientific Police of the State of Sao Paulo. After the screening, samples were confirmed for the presence of BZO-HEXOXIZID using chromatography gas—mass spectrometry, Fourier-transform infrared spectroscopy and nuclear magnetic resonance techniques. Results Of the 53 samples analyzed, 25 contained only BZO-HEXOXIZID and 28 with mixtures, of which 11 with the CB1 agonist ADB-BUTINACA. Other substances were found in association such as cocaine and caffeine. Conclusions BZO-HEXOXIZID was detected in a series of seized materials for the first time in Brazil. Nevertheless, there are still unanswered questions regarding the use of this selective CB2 agonist as a drug of abuse.
  PubDate: 2022-10-08
  DOI: 10.1007/s11419-022-00646-6
Exposure to high concentrations of carbon dioxide during transporting a
cadaver preserved with dry ice inside an ambulance vehicle
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  PubDate: 2022-10-05
  DOI: 10.1007/s11419-022-00644-8
Correction to: Postmortem histopathology and detection of venom by ELISA
following suicide by cobra (Naja kaouthia) envenomation
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  PubDate: 2022-09-27
  DOI: 10.1007/s11419-022-00642-w
Evaluation of decarboxylation efficiency of Δ9-tetrahydrocannabinolic
acid and cannabidiolic acid by UNODC method
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  Abstract: Purpose Decarboxylation of Δ9-tetrahydrocannabinolic acid (Δ9-THCA) to Δ9-tetrahydrocannabinol (Δ9-THC) by heating is a common method for determining total Δ9-THC. In the manual for cannabis identification and analysis, the United Nations Office on Drugs and Crime (UNODC) proposed decarboxylation conditions. Although the manual’s primary analytical target is Δ9-THC, some reports also quantified cannabidiol (CBD). The authors assessed the efficiency of decarboxylation of Δ9-THCA and cannabidiolic acid (CBDA), a carboxylated form of CBD, under four decarboxylation conditions, including the UNODC condition. Methods Δ9-THCA and CBDA were heated in 2-mL glass vials at 150 °C for 12 min after the following treatment: condition A involves the addition of ethanol without capping, condition B involves non addition of solvent without capping, condition C involves non addition of solvent with capping, and condition D (UNODC condition) involves the addition of 0.5 mg/mL tribenzylamine (TBA) in ethanol without capping. The residue after heating was dissolved in methanol and then analyzed by high-performance liquid chromatography. Results The production of Δ9-THC and CBD was low (≤ 10.1%) under conditions A and B. Under condition C, Δ9-THC production was increased (53.4%), but CBD production was hardly improved (11.7%). Under condition D, Δ9-THC and CBD production dramatically increased to 83.2 and 71.0%, respectively. Conclusions These findings indicated that TBA improved the production of Δ9-THC and CBD from their carboxylated forms; however, even in the presence of TBA, their production did not reach 100%. Forensic toxicologists should understand the effectiveness and limitations of decarboxylation under the UNODC condition.
  PubDate: 2022-09-23
  DOI: 10.1007/s11419-022-00645-7
Analysis of 2,5-dimethoxy-amphetamines and 2,5-dimethoxy-phenethylamines
aiming their determination in biological matrices: a review
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  Abstract: Purpose The present review aims to provide an overview of methods for the quantification of 2,5-dimethoxy-amphetamines and -phenethylamines in different biological matrices, both traditional and alternative ones. Methods A complete literature search was carried out with PubMed, Scopus and the World Wide Web using relevant keywords, e.g., designer drugs, amphetamines, phenethylamines, and biological matrices. Results Synthetic phenethylamines represent one of the largest classes of “designer drugs”, obtained through chemical structure modifications of psychoactive substances to increase their pharmacological activities. This practice is also favored by the fact that every new synthetic compound is not considered illegal by existing legislation. Generally, in a toxicological laboratory, the first monitoring of drugs of abuse is made by rapid screening tests that sometimes can occur in false positive or false negative results. To reduce evaluation errors, it is mandatory to submit the positive samples to confirmatory methods, such as gas chromatography or liquid chromatography combined to mass spectrometry, for a more specific qualitative and quantitative analysis. Conclusions This review highlights the great need for updated comprehensive analytical methods, particularly when analyzing biological matrices, both traditional and alternative ones, for the search of newly emerging designer drugs.
  PubDate: 2022-09-14
  DOI: 10.1007/s11419-022-00638-6
Short-term stability of a small amount of neat
Δ9-tetrahydrocannabinol
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  PubDate: 2022-09-13
  DOI: 10.1007/s11419-022-00641-x