Analytical findings in a non-fatal intoxication with the synthetic cannabinoid 5F-ADB (5F-MDMB-PINACA): a case report

The case report centres on analytical findings from a spice sample (mixed with tobacco (as a cigarette) for consumption), and its corresponding plasma sample, smoked by a 31-year-old man who was attended by emergency services following collapse. The man was fully conscious and cooperative during initial medical treatment. Suddenly, he suffered a complete loss of self-control, whereupon the police was notified. The man encountered the police officers when exiting the apartment, at which point he threatened them with clenched fists and reached for a plant bucket in order to strike out in the direction of the officers. At the trial, he described himself as confused and as being completely overwhelmed, having lost self-control, suffered a panic attack and just wanted to get out the situation. Furthermore, he stated that he had no recollection of the incident. He feared death due to palpitations, heart pain, dizziness and repetitive anxiety states. Routine systematic as well as extended toxicological analysis of the plasma sample, taken approximately 2 h after the incident, confirmed the use of cannabis and spice. Plasma concentrations of THC, OH-THC and THC-COOH were 8.0 mu g/L, 4.0 mu g/L and 147 mu g/L, respectively. Furthermore, analysis confirmed uptake of 5F-ADB (5F-MDMB-PINACA) via detection of both 5F-ADB and the 5F-ADB N-(5-OH-pentyl) metabolite. The spice sample additionally contained 5F-MDMB-PICA, which was not detected in the plasma sample. A differentiation between a possible co-use and a recent use of cannabis was not possible. In summary, this case once more underlines the health risks of spice use

Poisoning by addictive substances, laboratory tests, and forensic medical death clarification in the case of poisoning

Clinical-toxicological investigations are very helpful for the detection and assessment of the severity of questionable narcotics intoxications. In some cases, an initial case of clinical poisoning then progresses in the further course to a case of forensic relevance (for example after deliberate poisoning e.g, with knock-out drugs or with intend to commit murder, or in cases of intoxication in connection with a criminal offense). The specifics and problems of the analytical detection of these substances in clinical and forensic cases are explained with regard to the presented narcotic drugs. The information used comes from data from our own examination material and data from the literature. The spectrum of addictive substances has changed significantly in recent years. While established methods of detection are available for alcohol and classic drugs of abuse, new drugs with potential for abuse (such as methylphenidate, pregabalin) or NPS, GHB, GBL, and 4-BD cannot be detected by conventional methods of immunochemistry in combination with chromatographic methods such as GC-MS and HPLC-DAD. An improvement in the measurement equipment for specialised laboratories performing such investigations is therefore required in order to be able to adequately care for patients and to clarify criminal offenses. In the interests of legal certainty, it is important for offenders, in the case of a foreign substance being supplied to a victim, to assume that it can also be proven. In addition, with regard to the reliability of officially stated prevalence data for narcotic drugs in drug-related deaths, greater safety should be sought in the collection of all relevant substances

Modafinil in Forensic and Clinical Toxicology-Case Reports, Analytics and Literature

Modafinil is used because of its wakefulness-promoting properties for treatment of diseases associated with extreme sleepiness (i.e., narcolepsy). Additionally, it is misused as a cognitive enhancer to increase alertness and to improve concentration. We present modafinil concentrations in serum samples in five cases of our routine work measured by high-performance liquid chromatography coupled with a photo diode array detector after solid-phase extraction. One sample was analyzed for clinical toxicology purposes. The other four were investigated for the police: three cases of driving under the influence of drugs and one case of bodily harm. Sample preparation consisted of solid-phase extraction using Bond Elut (R) C18 columns. Papaverine was used as internal standard. Chromatographic separation was carried out using a Polaris C18-A column in an isocratic run. Wavelengths used for UV-detection were 220 nm for modafinil and 239 nm for the internal standard, respectively. The method was validated with a reduced validation design for rare analytes. A six-point-calibration from 0.5 to 5.0 mg/L, covering the therapeutic range (0.9-3.3 mg/L), was used for quantification. Concentrations in serum were in the range of 1.3 to similar to 34 mg/L (median: 3.6 mg/L; mean: 9.0 mg/L). To our knowledge, there are only few publications concerning the serum concentrations of modafinil in cases of (suspected) misuse, forensic cases or intoxications. In our discussion, the serum concentrations we determined are compared with the levels described in the literature so far

Swollen Lips After a Night of Partying-An Allergic Reaction to Ecstasy?

Ecstasy (MDMA) is a mood-lifting drug with numerous somatic side effects, for example, dehydration or continuous chewing and biting. We describe the case of a young woman who underwent a forensic medical examination for suspected sexual assault. She claimed to have suffered from a memory lapse, and she had a painful swelling of her lips with a plaque-like coating on her lips and buccal mucosa. The attending physician suspected that these findings might have been caused by strong sucking pressure on her lips within the context of a sexual assault. A toxicological examination of a blood specimen verified that she had been under the influence of an extremely high dose of ecstasy (1.456 mg/L MDMA and 0.0213 mg/L MDA). Pursuant to the forensic medical assessment, the described findings on her lips, and buccal mucosa were interpreted as an allergic and mechanical reaction (through continuous chewing and biting) to ecstasy

Alcohol Biomarkers in Clinical and Forensic Contexts

Background: Biomarkers of alcohol consumption are important not only in forensic contexts, e.g., in child custody proceedings or as documentation of alcohol abstinence after temporary confiscation of a driver's license. They are increasingly being used in clinical medicine as well for verification of abstinence or to rule out the harmful use of alcohol. Methods: This review is based on pertinent publications that were retrieved by a selective literature search in PubMed concerning the direct and indirect alcohol markers discussed here, as well as on the authors' experience in laboratory analysis and clinical medicine. Results: Alongside the direct demonstration of ethanol, the available markers of alcohol consumption include the classic indirect markers carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and mean corpuscular volume (MCV) as well as direct alcohol markers such as ethyl glucuronide (EtG) and ethyl sulfate (EtS) in serum and urine and EtG and fatty acid ethyl esters (FAEE) in hair. Phosphatidylethanol (PEth) is a promising parameter that complements the existing spectrum of tests with high specificity (48-89%) and sensitivity (88-100%). In routine clinical practice, the demonstration of positive alcohol markers often leads patients to admit previously denied alcohol use. This makes it possible to motivate the patient to undergo treatment for alcoholism. Conclusion: The available alcohol biomarkers vary in sensitivity and specificity with respect to the time period over which they indicate alcohol use and the minimum extent of alcohol use that they can detect. The appropriate marker or combination of markers should be chosen in each case according to the particular question that is to be answered by laboratory analysis

Accidental intoxication by outdoor and garden plants. Data from two German poison centres

Background and objectivesAccidental exposure of children to plants occurs often and results in numerous calls to poison centres.The aim of this study was to identify outdoor plants that led to moderate or severe poisoning after accidental exposure and to identify patterns of paediatric plant exposures.Materials and methodsHuman exposure data on accidental exposures provided by two German poison centres were retrospectively evaluated regarding the number and the routes of exposure. Special attention was turned to the kind and severity of symptoms. Based on these data amodified Litovitz factor was calculated.ResultsOut of 42,344 confirmed exposures to 227 plant species, 39,346 (93%) were asymptomatic, 2415 (5.7%) experienced minor, 580 (1.3%) moderate and 3 (0.007%) severe symptoms. Twenty-sixplant genera were responsible for 70% of all exposures. Only eight of these plants (Arum spec., Laburnum anagyroides, Narcissus spec., Phaseolus vulgaris/coccineus, Prunus laurocerasus, Sambucus spec., Taxus baccata, Thuja spec.) led to at least moderate symptoms. Accidental exposure of children aged 0.5-5years was mainly by oral ingestion (98%) and involved mostly fruits (60%).ConclusionsExposure data collected by poison centres are very useful for hazard identification of outdoor plants. The data give acomprehensive overview of observed symptoms, which offers valuable instruments for use in clinical practice

Simultaneous quantification of THC-COOH, OH-THC, and further cannabinoids in human hair by gas chromatography-tandem mass spectrometry with electron ionization applying automated sample preparation

The detection of Delta(9)-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in hair, for the purpose of identifying cannabis consumption, is conducted in many forensic laboratories. Since external contamination of hair with these cannabis components cannot be excluded, even after hair decontamination, only the detection of THC metabolites such as 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THC-COOH) or 11-hydroxy-Delta(9)-tetrahydrocannabinol (OH-THC), is considered to prove cannabis consumption. At present, testing for THC metabolites is not standard practice due to its analytical complexity. For these reasons, we developed a novel method for the detection of THC-COOH and OH-THC as well as THC, CBD, and CBN in one single analytical run using gas chromatography-tandem mass spectrometry (GC-MS/MS) with electron ionization. After manual hair washing and grinding, sample preparation was fully automated, by means of a robotic autosampler. The hair extraction took place by digestion with sodium hydroxide. A solid-phase extraction (SPE) was chosen for sample clean-up, using a mixed-mode anion exchange sorbent. Derivatization of all analytes was by silylation. The method has been fully validated according to guidelines of the Society of Toxicological and Forensic Chemistry (GTFCh), with a limit of detection (LOD) of 0.2 pg/mg for THC-COOH and OH-THC and 2 pg/mg for THC, CBD and CBN, respectively, thus fulfilling the Society of Hair Testing (SoHT) recommendations. The validated method has been successfully applied to our routine forensic case work and a summary of data from authentic hair samples is given, as well as data from proficiency tests

Characteristics and dose-effect relationship of clinical gamma-hydroxybutyrate intoxication: A case series

Gamma-Hydroxybutyrate (GHB) overdoses cause respiratory depression, coma, or even death. Symptoms and severity of poisoning depend on blood-concentrations and individual factors such as tolerance. A retrospective case study was conducted, evaluating GHB intoxication cases. GHB-concentrations in blood and urine were determined by gas chromatography-mass spectrometry (GC-MS) along with, in part, via enzymatic assay. GHB-concentrations, demographic data, and additional drug use, as well as specific clinical information, were evaluated. The correlation between GHB-levels in blood and associated symptoms were examined. In total, 75 cases originating from the Emergency Departments (EDs) of Hamburg and surrounding hospitals were included. Fifty-four of the patients (72%) were male. The mean GHB-concentration in blood was 248 mg/L (range 21.5-1418 mg/L). Out of the group with detailed clinical information (n = 18), the comatose group (n = 10/18) showed a mean of 244 mg/L (range 136-403 mg/L), which was higher than that of the somnolent and awake patients. Of the comatose collective, 70% (n = 7) showed co-use of one or more substances, with the additional use of cocaine being the most frequently detected (n = 5). In conclusion, a moderate dose-effect relationship was observed, although, there was some overlap in dosage concentration levels of GHB in awake and comatose patients. In GHB-intoxication cases, co-use was common as were clinical effects such as acidosis, hypotension, and impact on the heart rate. Timely analytical determination of the GHB-concentration in blood could support correct diagnosis of the cause of unconsciousness

Quantification of direct-acting oral anticoagulants: Application of a clinically validated liquid chromatography-tandem mass spectrometry method to forensic cases

In certain forensic cases, a quantification of direct-acting oral anticoagulants (DOACs) can be necessary. We evaluate the applicability of a previously described liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology for the determination of DOACs in plasma to postmortem specimen. Postmortem internal quality control (PIQC) samples were prepared in pooled blank postmortem heart blood, femoral blood, cerebrospinal fluid (CSF), and urine as well in plasma. To examine the application of the clinical method to forensic cases, the main validation parameters were reinvestigated using PIQC samples. Postmortem samples of 12 forensic cases with evidence of previous rivaroxaban intake and unknown bleeding disorders were analyzed. Interday variability remained within the acceptance criterion of +/- 15%. Matrix effects were comparable in blank plasma and postmortem matrix extracts. After 4 weeks of storage in the refrigerator, no relevant decrease of DOACs was evident. After 96 h of storage at room temperature, a slight decrease in edoxaban concentration was observed in CSF and urine, while plasma edoxaban decreased by about 50%. Median (range) rivaroxaban concentrations determined in specimen of forensic cases were as follows: heart blood (n = 6), 17.2 ng/ml (<LOQ, 56.6 ng/ml); femoral blood (n = 12), 27.6 ng/ml (<LOQ, 110.5 ng/ml); CSF (n = 7), 11.7 ng/ml (<LOQ, 17.5 ng/ml); urine (n = 6), 275.7 ng/ml (14.5-870.9 ng/ml). The median heart/femoral blood rivaroxaban ratio was 1.2 (n = 5). Exemplary, a forensic case with detection of edoxaban in femoral blood, CSF, and urine, is presented. DOACs can be detected in postmortem heart and femoral blood, CSF, and urine specimen by LC-MS/MS. Based on limited forensic cases, no significant redistribution was evident for rivaroxaban, which was found at highest concentrations in urine