On the impact of cannabis consumption on traffic safety: a driving simulator study with habitual cannabis consumers.

To contribute to the ongoing discussion about threshold limits of Δ9-tetrahydrocannabinol (THC) in road traffic, a driving simulator study with 15 habitually cannabis consuming test persons was conducted. Probands were tested on different routes after consumption of a maximum of three cannabis joints, each containing 300 µg THC/kg body weight (sober testing as well as testing directly, 3 and 6 h after cannabis consumption). Accompanying the drives, medical examinations including a blood sampling were performed. Driving faults and distinctive features in the medical examinations were allocated certain penalty points, which were then summed up and evaluated using the ANOVA model. The results showed that very high CIF values > 30 as well as serum THC concentrations > 15 ng/ml significantly increased the number of penalty points, but no direct correlation to the THC concentrations in serum and/or CIF values was detected. Instead, the point in time after cannabis consumption seems to play an important role concerning driving safety: significantly more driving faults were committed directly after consumption. Three hours after consumption, no significant increase of driving faults was seen. Six hours after consumption (during the so-called subacute phase), an increase of driving faults could be noted although not significant. Considering the limitation of our study (e.g. small test group, no placebo test persons, long lasting test situation with possible tiredness), further studies focusing on the time dependant impact of cannabis consumption on road traffic are required.

Clinical and Toxicological Profile of NBOMes: A Systematic Review.

BACKGROUND: NBOMes are a new class of potent hallucinogens widely present in illicit drugs. Little is known about this class of drugs, regarding its detection and clinical manifestations of intoxication. OBJECTIVE: This study aims to enhance care involving NBOMes by reviewing the literature on their clinical manifestations and laboratorydetection. METHODS: A systematic review was performed on the clinical manifestations and laboratory tests of NBOMEs ingestion. Embase, Pubmed, PsycINFO, and Cochrane databases were employed in this analysis. RESULTS: Forty-five articles met the inclusion criteria out of the 2814 nonduplicated studies on the theme. Seventy case reports of intoxication were found in the analyzed articles (64.3% were men and 11.4% were women, mean age of 22.5). The technique most employed for NBOMes identification was chromatography of blood, urine, and oral fluids. Moreover, the studies identified 13 chemical structures differentfrom the NBOMes on their toxicological analyses.According to these studies, most of these drugs were ingested orally-nasal use was the second preferred administration route, followed by intravenous administration. CONCLUSION: Better identification of the clinicalmanifestations and laboratory profile of NBOMes is crucial to the recognition of intoxication as well as to its effective treatment.

8ß-OH-THC and 8ß,11-diOH-THC-minor metabolites with major informative value?

The ∆9-tetrahydrocannabinol (THC) metabolites 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC are mentioned in the literature as potential blood markers of recent cannabis use. However, the formation of these metabolites in in vivo detectable concentrations has been described controversially. Therefore, the aim of this study was to verify the in vivo metabolism of 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC in order to evaluate their potential as blood markers of recent cannabis use. First, we developed and validated a solid-phase-extraction method coupled with gas chromatography-mass spectrometry in order to enable the selective and very sensitive determination of 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC. The application of this method in the analysis of 70 authentic plasma samples of cannabis users revealed positive results for both analytes. We detected 8ß-hydroxy-THC in three and 8ß,11-dihydroxy-THC in 37 out of the 70 analyzed samples. For 8ß-hydroxy-THC, all of the three positive results were below the limit of quantification (LOQ; 0.3 ng/mL) but above the limit of detection (LOD; 0.2 ng/mL). For 8ß,11-dihydroxy-THC, only two positive results were below the LOQ (0.4 ng/mL) but above the LOD (0.3 ng/mL); the remaining 35 were quantified. Hence, we were able to prove the in vivo metabolism from THC to both 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC in detectable concentrations. The quantitative comparison of 8ß-hydroxy-THC and 8ß,11-dihydroxy-THC with the main cannabinoids THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC revealed no further informative value for 8ß-hydroxy-THC regarding the last time of cannabis consumption. However, the detectability from 8ß,11-dihydroxy-THC compared to 11-hydroxy-THC suggests a shorter detection time for 8ß,11-dihydroxy-THC and thereby a promising application of this metabolite as a blood marker of recent cannabis use.

First Time View on Human Metabolome Changes after a Single Intake of 3,4-Methylenedioxymethamphetamine in Healthy Placebo-Controlled Subjects.

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is widely consumed recreationally. Little is known about its effects on the human metabolome. Mapping biochemical changes after drug exposure can complement traditional approaches by revealing potential biomarkers of organ toxicity or discovering new metabolomic features in a time- and dose-dependent manner. We aimed to analyze for the first time plasma samples from a randomized, double-blind, placebo-controlled crossover study in healthy adults to explore changes in endogenous plasma metabolites following a single intake of MDMA. Plasma samples from 15 subjects taken at four different time points were analyzed with the commercially available AbsoluteIDQ kit (Biocrates). Time series analysis revealed a total of nine metabolites, which showed a significant concentration change after MDMA administration compared with placebo. Paired t tests of the single time points showed statistically significant concentration changes mainly of glycerophospholipids and the metabolic ratio of methionine-sulfoxide over methionine. Changes of this metabolic ratio may be indicative for changes in systemic oxidative stress levels, and the increased amount of glycerophospholipids could be interpreted as an upregulation of energy production. Baseline samples within the experimental study design were crucial for evaluation of metabolomics data as interday individuality within subjects was high otherwise resulting in overestimations of the findings.

Serotonergic psychedelics temporarily modify information transfer in humans.

BACKGROUND: Psychedelics induce intense modifications in the sensorium, the sense of "self," and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects. METHODS: Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy, a nonlinear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine. RESULTS: The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. Transfer entropy analysis showed that frontal sources decreased their influence over central, parietal, and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced. CONCLUSIONS: These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain.

Pharmacokinetics and Concentration-Effect Relationship of Oral LSD in Humans.

BACKGROUND: The pharmacokinetics of oral lysergic acid diethylamide are unknown despite its common recreational use and renewed interest in its use in psychiatric research and practice. METHODS: We characterized the pharmacokinetic profile, pharmacokinetic-pharmacodynamic relationship, and urine recovery of lysergic acid diethylamide and its main metabolite after administration of a single oral dose of lysergic acid diethylamide (200 µg) in 8 male and 8 female healthy subjects. RESULTS: Plasma lysergic acid diethylamide concentrations were quantifiable (>0.1 ng/mL) in all the subjects up to 12 hours after administration. Maximal concentrations of lysergic acid diethylamide (mean±SD: 4.5±1.4 ng/mL) were reached (median, range) 1.5 (0.5-4) hours after administration. Concentrations then decreased following first-order kinetics with a half-life of 3.6±0.9 hours up to 12 hours and slower elimination thereafter with a terminal half-life of 8.9±5.9 hours. One percent of the orally administered lysergic acid diethylamide was eliminated in urine as lysergic acid diethylamide, and 13% was eliminated as 2-oxo-3-hydroxy-lysergic acid diethylamide within 24 hours. No sex differences were observed in the pharmacokinetic profiles of lysergic acid diethylamide. The acute subjective and sympathomimetic responses to lysergic acid diethylamide lasted up to 12 hours and were closely associated with the concentrations in plasma over time and exhibited no acute tolerance. CONCLUSIONS: These first data on the pharmacokinetics and concentration-effect relationship of oral lysergic acid diethylamide are relevant for further clinical studies and serve as a reference for the assessment of intoxication with lysergic acid diethylamide.

Internet-purchased ibogaine toxicity confirmed with serum, urine, and product content levels.

UNLABELLED: Ibogaine, a psychotropic indole alkaloid, is gaining popularity among medical subcultures for its purported anti addictive properties. Its use has been associated with altered mental status, ataxia, gastrointestinal distress, ventricular arrhythmias, and sudden and unexplained deaths.Its pharmacokinetics in toxic states is not well understood. Case report:A 33-year-old man overdosed on ibogaine in an attempt to quit his use of heroin. He developed altered state of consciousness, tremor, ataxia,nausea, vomiting, and transient QT interval prolongation, which all remitted as he cleared the substance. Ibogaine was confirmed in his urine and serum with a peak serum concentration of 377 ng/mL. Nonlinear elimination kinetics and a formula match to its active metabolite noriobgaine were observed as well. CONCLUSION: This case presents the unique description of serial serum concentrations as well as urine and product-confirmed ibogaine toxicity with transient toxin-related QT interval prolongation.

Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.

Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).

Pathological findings in 2 cases of fatal 25I-NBOMe toxicity.

The research compound 25I-NBOMe, also known as CIMBI-5 or INBMeO, was created in academic laboratories as a potent serotonin 2A receptor agonist. Because of its high affinity and ambiguous legal status, recreational drug enthusiasts have used this compound as a powerful alternative to other hallucinogenic drugs such as lysergic acid diethylamide. We report 2 deaths after 25I-NBOMe ingestion by decedents who attended separate "rave" parties. The first case involved a 21-year-old male who admitted taking "acid" to his friend. A sudden violent rage caused him to flail about, and he subsequently became unresponsive. The postmortem examination revealed numerous external injuries that were consistent with physical aggression. The second case involved a 15-year-old female who was socializing outside a rave party, became ill, and rapidly deteriorated as her friend transported her to the hospital. The postmortem assessment was similar to the first case in that external contusions featured prominently. Comprehensive toxicology screens in both cases revealed only evidence of marijuana use. A deeper analysis using time-of-flight mass spectrometry revealed the presence of 25I-NBOMe, which was further confirmed by tandem-mass spectrometry. The behavior and injuries in these cases reveal a consistent pattern preceding fatal 25I-NBOMe toxicity.

Addressing a major interference in the quantification of psilocin in mouse plasma: Development of a validated liquid chromatography tandem mass spectrometry method.

Psilocybin is a psychedelic compound found in some hallucinogenic "magic mushrooms". Psilocin is the active metabolite of Psilocybin, and it is the subject of several studies for the treatment of psychological disorders, such as anxiety, depression, and post-traumatic stress disorder. As such, the pharmacokinetic properties of psilocin should be evaluated to ensure its safety and efficacy as part of the drug development process. Based on the previously published studies, reversed-phase liquid chromatography (LC) was tested for psilocin quantification. The analysis, however, showed a major interference in mouse plasma that was not, to the best of our knowledge, reported previously. We, therefore, aimed to identify and separate the interference, using various chromatographic columns, mobile phase conditions, and mass spectrometers (MS) instruments. Chromatographic separation was achieved on an ultra high performance liquid chromatography (UHPLC) system, and a quadrupole-linear ion trap equipped with an electrospray ionization (ESI) source was used in positive ion mode with multiple reaction monitoring (MRM). Several chromatographic conditions and column chemistries, including C-18 and Phenyl-hexyl were initially tested, and failed to separate the interference. Exact mass measurement and MS/MS analysis were used to determine the structure of the interfering compound, which was confirmed to be tryptophan. Using the identified structure of the interfering compound, a fast and reliable hydrophilic interaction liquid chromatography (HILIC)-MS/MS method was developed and validated, that was capable of separating psilocin from the interference while achieving a 0.5 ng/ml lower limit of quantification (LLOQ). The validated method was successfully applied to a pharmacokinetic study where psilocin was orally administered to C57BL/6 mouse subjects. Psilocin concentration in all the analyzed mouse plasma samples was successfully determined.

The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.

OBJECTIVE: Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine. METHODS: The study was performed in 14 subjects with OUD. They received a single dose of 10mg/kg ibogaine hydrochloride. Plasma PKs of ibogaine, noribogaine, and noribogaine glucuronide were obtained during 24 h. Cytochrome P450 isoenzyme 2D6 (CYP2D6) genotyping was performed. The PKs were analyzed by means of nonlinear mixed effects modeling and related with corrected QT interval (QTc) prolongation, cerebellar ataxia, and opioid withdrawal severity. RESULTS: The PK of ibogaine were highly variable and significantly correlated to CYP2D6 genotype (p < 0.001). The basic clearance of ibogaine (at a CYP2D6 activity score (AS) of 0) was 0.82 L/h. This increased with 30.7 L/h for every point of AS. The relation between ibogaine plasma concentrations and QTc was best described by a sigmoid Emax model. Spearman correlations were significant (p < 0.03) for ibogaine but not noribogaine with QTc (p = 0.109) and cerebellar effects (p = 0.668); neither correlated with the severity of opioid withdrawal symptoms. CONCLUSIONS: The clearance of ibogaine is strongly related to CYPD2D6 genotype. Ibogaine cardiac side effects (QTc time) and cerebellar effects are most likely more driven by ibogaine rather than noribogaine. Future studies should aim at exploring lower doses and/or applying individualized dosing based on CYP2D6 genotype.

Determination of psilocin, bufotenine, LSD and its metabolites in serum, plasma and urine by SPE-LC-MS/MS.

A validated method for the simultaneous determination of psilocin, bufotenine, lysergic acid diethylamide and its metabolites in serum, plasma and urine using liquid chromatography-electrospray ionization/tandem mass spectrometry was developed. During the solid-phase extraction procedure with polymeric mixed-mode cation exchange columns, the unstable analytes were protected by ascorbic acid, drying with nitrogen and exclusion of light. The limits of detection and quantitation for all analytes were low. Recovery was ≥86 % for all analytes and no significant matrix effects were observed. Interday and intraday imprecisions at different concentrations ranged from 1.1 to 8.2 % relative standard deviation, bias was within ±5.3 %. Processed samples were stable in the autosampler for at least 2 days. Furthermore, freeze/thaw and long-term stability were investigated. The method was successfully applied to authentic serum and urine samples.

Oral fluid/plasma cannabinoid ratios following controlled oral THC and smoked cannabis administration.

Oral fluid (OF) is a valuable biological alternative for clinical and forensic drug testing. Evaluating OF to plasma (OF/P) cannabinoid ratios provides important pharmacokinetic data on the disposition of drug and factors influencing partition between matrices. Eleven chronic cannabis smokers resided on a closed research unit for 51 days. There were four 5-day sessions of 0, 30, 60, and 120 mg oral ∆(9)-tetrahydrocannabinol (THC)/day followed by a five-puff smoked cannabis challenge on Day 5. Each session was separated by 9 days ad libitum cannabis smoking. OF and plasma specimens were analyzed for THC and metabolites. During ad libitum smoking, OF/P THC ratios were high (median, 6.1; range, 0.2-348.5) within 1 h after last smoking, decreasing to 0.1-20.7 (median, 2.1) by 13.0-17.1 h. OF/P THC ratios also decreased during 5-days oral THC dosing, and after the smoked cannabis challenge, median OF/P THC ratios decreased from 1.4 to 5.5 (0.04-245.6) at 0.25 h to 0.12 to 0.17 (0.04-5.1) at 10.5 h post-smoking. In other studies, longer exposure to more potent cannabis smoke and oromucosal cannabis spray was associated with increased OF/P THC peak ratios. Median OF/P 11-nor-9-carboxy-THC (THCCOOH) ratios were 0.3-2.5 (range, 0.1-14.7) ng/µg, much more consistent in various dosing conditions over time. OF/P THC, but not THCCOOH, ratios were significantly influenced by oral cavity contamination after smoking or oromucosal spray of cannabinoid products, followed by time-dependent decreases. Establishing relationships between OF and plasma cannabinoid concentrations is essential for making inferences of impairment or other clinical outcomes from OF concentrations.

Chronic cannabis abuse, delta-9-tetrahydrocannabinol and thyroid function.

OBJECTIVE: The aim of this study was to obtain rather rare information about the influence of chronic cannabis abuse on thyroid function. METHODS: Thyroid function tests (TSH, total T3, free T4) of 39 chronic cannabis-dependent subjects (ICD-10) were determined at admission (for in-patient detoxification). In a subgroup, serum levels of thyroid hormones were correlated with the serum levels of delta-9-tetrahydrocannabinol (THC, N=24) and its major metabolites, THC-OH (N=16) and THC-COOH (N=24). RESULTS: All of the tested patients were found to have TSH, total T3 and free T4 levels within the population reference range. The levels of thyroid hormones did not correlate significantly with levels of THC, THC-OH or THC-COOH in serum. CONCLUSION: These results argue against a relevant influence of chronic cannabis intake on thyroid function in humans.

[Suicide under the influence of "magic mushrooms"]. / Suizid unter Psilocin-Einfluss.

Psilocybin/psilocin from so-called psychoactive mushrooms causes hallucinogenic effects. Especially for people with mental or psychiatric disorders ingestion of magic mushrooms may result in horror trips combined with the intention of self-destruction and suicidal thoughts. Automutilation after consumption of hallucinogenic mushrooms has already been described. Our case report demonstrates the suicide of a man by self-inflicted cut and stab injuries. A causal connection between suicidal behaviour and previous ingestion of psychoactive mushrooms is discussed.

Catecholaminergic polymorphic ventricular tachycardia found in an adolescent after a methylenedioxymethamphetamine and marijuana-induced cardiac arrest.

OBJECTIVE: To illustrate the challenges of managing patients with acute, undiagnosed arrhythmias through a case that demonstrates a possible association between catecholaminergic polymorphic ventricular tachycardia, a genetically determined severe arrhythmia disorder that often presents as either syncope or sudden death, and 3,4-Methylenedioxymethamphetamine ("Ecstasy") combined with marijuana, which are often considered safe drugs by users. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A 15-yr-old male collapsed suddenly after ingesting an unknown substance and smoking marijuana. He was successfully resuscitated by first-responder chest compressions and rescue breaths along with a single 100-J shock by paramedics. He was intubated and transferred to a pediatric intensive care unit. Initial cardiac workup was negative but severe instability on vasopressors and a family history of intermittent palpitations and syncope in his brother raised suspicion for catecholaminergic polymorphic ventricular tachycardia. Identification of the unknown substance required coordination with a toxicology laboratory. INTERVENTIONS: The patient had extremely labile cardiovascular responses to vasopressors. On day 5, his blood pressure was stable and he was extubated. A full cardiac workup, including a catheterization (preadmission to pediatric intensive care unit), electrocardiogram, cardiac magnetic resonance imaging were done to screen out most structural arrythmogenic diseases. A specific genetic test for catecholaminergic polymorphic ventricular tachycardia was sent. MEASUREMENTS AND MAIN RESULTS: The patient's methylenedioxymethamphetamine blood level was 87 ng/mL approximately 12 hrs after ingestion. Given the 3-8 hr half-life of methylenedioxymethamphetamine, it is likely that levels were toxic at the time of ingestion (>110 ng/mL). Marijuana may have provided a synergistic critical catecholamine release to trigger an arrhythmia. Genetic testing showed a ryanodine receptor-2 mutation that was consistent with catecholaminergic polymorphic ventricular tachycardia. CONCLUSIONS: While an initial cardiac workup for an acute, undiagnosed arrhythmia may be negative, family history may be a simple, essential component of patient management and disease diagnosis. This case demonstrates a possible association between methylenedioxymethamphetamine, marijuana, and catecholaminergic polymorphic ventricular tachycardia. All genetic and structural arrythmogenic disorders should be considered when working up a patient with presumed toxin-induced arrhythmias.

The neuropharmacology of prolactin secretion elicited by 3,4-methylenedioxymethamphetamine ("ecstasy"): a concurrent microdialysis and plasma analysis study.

3,4-methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine that is widely abused as the street drug "ecstasy". Racemic MDMA (S,R(+/-)-MDMA) and its stereoisomers elicit complex spectrums of psychobiological, neurochemical, and hormonal effects. In this regard, recent findings demonstrated that S,R(+/-)-MDMA and its stereoisomer R(-)-MDMA elicit increases in striatal extracellular serotonin levels and plasma levels of the hormone prolactin in rhesus monkeys. In the present mechanistic study, we evaluated the role of the serotonin transporter and the 5-HT(2A) receptor in S,R(+/-)-MDMA- and R(-)-MDMA-elicited prolactin secretion in rhesus monkeys through concurrent microdialysis and plasma analysis determinations and drug interaction experiments. Concurrent neurochemical and hormone determinations showed a strong positive temporal correlation between serotonin release and prolactin secretion. Consistent with their distinct mechanisms of action and previous studies showing that the serotonin transporter inhibitor fluoxetine attenuates the behavioral and neurochemical effects of S,R(+/-)-MDMA, pretreatment with fluoxetine attenuated serotonin release elicited by either S,R(+/-)-MDMA or R(-)-MDMA. As hypothesized, at a dose that had no significant effects on circulating prolactin levels when administered alone, fluoxetine also attenuated prolactin secretion elicited by S,R(+/-)-MDMA. In contrast, combined pretreatment with both fluoxetine and the selective 5-HT(2A) receptor antagonist M100907 was required to attenuate prolactin secretion elicited by R(-)-MDMA, suggesting that this stereoisomer of S,R(+/-)-MDMA elicits prolactin secretion through both serotonin release and direct agonism of 5-HT(2A) receptors. Accordingly, these findings inform our understanding of the neuropharmacology of both S,R(+/-)-MDMA and R(-)-MDMA and the regulation of prolactin secretion.

A validated method for quantitation of psilocin in plasma by LC-MS/MS and study of stability.

A liquid chromatography-electrospray ionization/tandem mass spectrometry method for the quantitation of psilocin in plasma is presented. Sample workup was performed with mixed-mode solid-phase extraction using ascorbic acid and nitrogen for drying to protect the unstable analyte. Calibration curves were linear from 2 to 100 ng/mL, and no selectivity problems occurred. The limit of detection was 0.1 ng/mL, and the limit of quantitation was 0.34 ng/mL. Recovery was >86% and matrix effects were <110%. Both were reproducible. Interday and intraday precisions at different concentrations were 1.5-4.3% relative standard deviation, bias within ±9%. Processed samples were stable in the autosampler for at least 26 h. Furthermore, the stability of psilocin in blood stored at different temperatures over various periods of time was investigated. Samples stored at room temperature showed a continuous decrease of analyte leading to a loss of about 90% after 1 week. Storage in the fridge improved sample stability significantly. Freezing of blood samples led to a not reproducible loss of psilocin.

[Resurgence in paramethoxamphetamine use. Review of poisonings and two recent cases study]. / Powrót do uzywania parametoksyamfetaminy. Przeglad zatruc i studium dwóch nowych przypadków.

Two recent cases of death due to p-methoxyamphetamine (PAM) intake, a methoxylated phenethylamine derivative, were described and compared with previous PMA related deaths that occurred in many countries. Following a review of the available literature from 1974 to 2011 three periods of resurgence of an unsuspected increase of lethal PMA causation were considered. Signs of intoxications, concentrations of PMA found in biological materials were discussed. Based on the case reports can be concluded the great number of victims were unconscious of taking PMA as substitute of MDMA. Two new methods for screening, identification and quantification of amphetamine derivatives in biosamples (blood and urine) using LC-MS/MS techniques were developed. The methods have proven to be appropriate for clinical and forensic toxicology purposes.

Measurement uncertainty in quantifying delta-9-tetrahydrocannabinol (THC) in blood using SPE and LC/MS/MS.

A method for the quantitative analysis of delta-9-tetrahydrocannabinol (THC, the main active ingredient of cannabis) in whole blood using solid phase extraction and LC/MS/MS has been developed. A bottom-up approach with method validation data was used to evaluate and estimate the measurement uncertainty (MU) of the analytical method. The sources of uncertainty were identified using a cause and effect diagram. The contribution of each uncertainty component was estimated and were combined to derive the overall uncertainty of the analytical method. The combined uncertainty was estimated to be 0.131 µg/L (<7%). At a 99.7% confidence level, the expanded uncertainty was 0.393 µg/L for a THC concentration of 2 µg/L in a whole blood sample. The calculations not only enable the laboratory to quantify the uncertainty associated with a quantitative result, but can also be used to identify the sources of uncertainty and determine if the analytical method can be improved. An open access Measurement Uncertainty Calculator (MUCalc) software has been developed using the method described in this paper.