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 µg/L, 4.0 µg/L and 147 µg/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.

Evidence for the transfer of methadone and EDDP by sweat to children's hair.

In cases where there is a question as to whether children have come into contact with drugs, examinations of their scalp hair are frequently carried out. Positive test results are often discussed in the forensic community due to the various possible modes via which drugs and their metabolites can be incorporated into the hair. These include drug uptake by the child (e.g. oral ingestion or inhalation), but also contamination of hair via contact with the sweat from drug users. In this study, the possibility of methadone and its metabolite EDDP being incorporated into children's hair by contact with sweat from persons undergoing opiate maintenance therapy (methadone) was examined. The transfer of methadone and EDDP via sweat from methadone patients (n = 15) to children's hair was simulated by close skin contact of drug-free children's hair, encased in mesh-pouches, for 5 days. Sweat-collecting patches (hereafter referred to as 'sweat patches') were applied to the test persons' skin. One strand of hair and one sweat patch were collected daily from each patient. Analyses were performed using GC-MS/MS (hair) and LC-MS/MS (serum, sweat patches). After 4 days of skin contact, methadone was detectable in the formerly drug-free hair strands in all 15 study participants. EDDP was detectable in 34 of 75 hair strands, with the maximum number of positive results (11 EDDP-positive hair strands) being detected after 5 days. These results show that transfer of methadone and EDDP to drug-free hair is possible through close skin contact with individuals taking part in methadone substitution programmes. A correlation between serum concentration, sweat concentration and substance concentration in hair strands could not be demonstrated, but a tendency towards higher concentrations due to longer contact time is clearly evident.

Revisited: Therapeutic and toxic blood concentrations of more than 1100 drugs and other xenobiotics.

In order to assess the significance of drug/substance levels measured in intensive care medicine and clinical and forensic toxicology as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. We revisited and expanded our 2012 compilation of therapeutic and toxic plasma concentration ranges as well as half-lives of now more than 1100 drugs and other xenobiotics.Data have been abstracted from original papers, text books, and previous compilations and have been completed with data collected in our own forensic and clinical toxicology laboratories. We compiled the data presented in the table and the corresponding annotations over the past 30+ years. A previous compilation was completely double-checked, revised, and updated, if necessary. In addition, more than 200 substances, especially drugs who have been introduced since 2012 to the market as well as illegal drugs and other xenobiotics which became known to cause intoxications were added. We carefully referenced all data. Moreover, the annotations providing details were updated and revised, when necessary.For more than 1100 drugs and other xenobiotics, therapeutic ("normal") and, if data was available, toxic, and comatose-fatal plasma/blood concentrations as well as elimination half-lives were compiled in a table.In case of intoxications, the blood concentration of the substance and/or metabolite better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications as well as to support forensic and clinical expert opinions.

[Poisoning by addictive substances, laboratory tests, and forensic medical death clarification in the case of poisoning]. / Vergiftungen durch Suchtstoffe, Laboruntersuchungen und rechtsmedizinische Todesfallaufklärung bei Vergiftungen.

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 4­BD 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.

[Poisonous plants-a new approach for assessing the risk of poisoning in small children]. / Risiko Pflanze ­ Ein neuer Ansatz zur Einschätzung des Vergiftungsrisikos für Kleinkinder.

BACKGROUND: Plant poisoning in small children (from 0.5 to <6 years of age) is the third most frequent cause for phone contact with a poison center. For prevention of poisonings, a list of poisonous plants that should not be planted close to playgrounds or other places frequently visited by children was published in 2000 by the Bundesanzeiger. This list has been reevaluated and updated by the "Toxicity of Plants" working group of the Committee of the Assessment of Intoxications at the Federal Institute of Risk Assessment (BfR). MATERIALS AND METHODS: Relevant plants were taken from a recent publication. A literature search was conducted in PubMed concerning all plant poisonings in children and the toxic ingredients of plants. Also, monographs and the database POISINDEX were integrated in the evaluation. A classification was made for plants that after oral, dermal, or ocular contact of small quantities could cause severe, moderate, mild, or no intoxications in small children. RESULTS: Based on data of exposure and potentially toxic ingredients of the involved plants, a risk assessment was executed, which diverges from other publications because it concerns the actual basic risk of an intoxication. In total, 251 plants were reevaluated. For 11 plants, there was a high risk, for 32 a moderate, for 115 a mild, and for 93 plants no risk of intoxication could be determined. CONCLUSION: The new assessment of evaluating a toxicity risk for small children on the basis of exposure data and including the toxicity of ingredients allows for a more realistic assessment of the risk of poisoning with outdoor plants. In this way, infant exposure carrying a high risk of intoxication can be identified.

[Accidental intoxication by outdoor and garden plants : Data from two German poison centres]. / Akzidentelle Vergiftungen mit Gartenpflanzen und Pflanzen in der freien Natur : Daten aus zwei deutschen Giftinformationszentren.

BACKGROUND AND OBJECTIVES: Accidental 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 METHODS: Human 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 a modified Litovitz factor was calculated. RESULTS: Out 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-six plant 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 0.5-5 years was mainly by oral ingestion (98%) and involved mostly fruits (60%). CONCLUSIONS: Exposure data collected by poison centres are very useful for hazard identification of outdoor plants. The data give a comprehensive overview of observed symptoms, which offers valuable instruments for use in clinical practice.

Improved detection of alcohol consumption using the novel marker phosphatidylethanol in the transplant setting: results of a prospective study.

Phosphatidylethanol (PEth) is a new, highly specific alcohol marker. The aim of this study was to assess its diagnostic value in the liver transplant setting. In 51 pre- and 61 post-transplant patients with underlying alcoholic liver disease PEth, ethanol, methanol, carbohydrate-deficient transferrin (CDT), and ethyl glucuronide in urine (uEtG) and hair (hEtG) were tested and compared with patients' questionnaire reports. Twenty-eight (25%) patients tested positive for at least one alcohol marker. PEth alone revealed alcohol consumption in 18% of patients. With respect to detection of alcohol intake in the preceding week, PEth showed a 100% sensitivity. PEth testing was more sensitive than the determination of ethanol, methanol, CDT or uEtG alone [sensitivity 25% (confidence interval (CI) 95%, 7-52%), 25% (7-52%), 21% (6-45%) and 71% (41-91%), respectively], or ethanol, methanol and uEtG taken in combination with 73% (45-92%). Specificity of all markers was 92% or higher. Additional testing of hEtG revealed alcohol consumption in seven patients, not being positive for any other marker. Phosphatidylethanol was a highly specific and sensitive marker for detection of recent alcohol consumption in pre- and post-transplant patients. The additional determination of hEtG was useful in disclosing alcohol consumption 3-6 months retrospectively.

Endogenous gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens and further recommendation for interpretative cut-offs.

When interpreting gamma-hydroxybutyric acid (GHB) concentrations in post-mortem specimens, a possible increase in GHB concentrations because of post-mortem generation must be considered. In this study, endogenous GHB concentrations in post-mortem biological fluids were investigated. Additionally, we review post-mortem GHB concentrations already published in the literature. Heart and peripheral blood samples, cerebrospinal fluid, urine, and vitreous humor were collected from 64 autopsies in subjects where the cause of death excluded GHB exposure. Sample analysis was carried out either on the day of autopsy or later after immediate freezing and storage at -20 °C. GHB concentrations in venous blood samples (n = 61) were <0.6-28.7 mg/L (mean 11.9 mg/L; median 10.6 mg/L), <0.6-65.3 mg/L (mean 15.2 mg/L; median 12.8 mg/L) in heart blood (n = 56), <0.6-25.1 mg/L (mean 6.0 mg/L; median 3.8 mg/L) in urine (n = 50), <0.6-39.0 mg/L (mean 9.6 mg/L; median 7.5 mg/L), in vitreous humor (n = 54), and <0.6-24.0 mg/L (mean 4.2 mg/L; median 3.2 mg/L) in cerebrospinal fluid (n = 52). There was no significant difference between GHB concentrations in cases where there were signs of beginning putrefaction at the time of autopsy (n = 9) and cases without obvious signs of putrefaction. In one case with advanced putrefaction, the GHB concentration in venous blood was 32.7 mg/L. In conclusion, for post-mortem venous blood, urine, and cerebrospinal fluid, an interpretative cut-off of 30 mg/L for GHB concentrations is suggested in cases where GHB analysis is conducted on the day of sample collection at autopsy or if samples have been stored at -20 °C immediately after collection.

Determination of Ethyl Glucuronide in Hair for Detection of Alcohol Consumption in Patients After Liver Transplantation.

BACKGROUND: Early detection of alcohol misuse in orthotopic liver transplantation recipients is essential to offer patients support and prevent organ damage. Here, ethyl glucuronide, a metabolite of ethanol found in hair (hEtG), was evaluated for detection of alcohol consumption. METHODS: In 104 transplant recipients, 31 with underlying alcoholic liver disease (ALD) and 73 with non-ALD, hEtG was determined in addition to the alcohol markers urine EtG, blood ethanol, methanol, and carbohydrate-deficient transferrin. Results were compared with patients' self-reports in a questionnaire and with physicians' assessments. RESULTS: By physicians' assessments, 22% of the patients were suspected of consuming alcohol regularly, although only 6% of the patients acknowledged consumption of a moderate or high amount of alcohol. By testing all markers except for hEtG, alcohol consumption was detected in 7% of the patients. When hEtG testing was added to the assessment, consumption was detected in 17% of the patients. Hair-EtG determination alone revealed chronic alcohol consumption of >10 g/d in 15% of the patients. ALD patients had a positive hEtG result significantly more often than non-ALD patients did (32% versus 8%; P = 0.003). Also, the concentration of hEtG was higher in ALD patients (P = 0.049) and revealed alcohol abuse with consumption of >60 g ethanol per day in 23% of ALD and 3% of non-ALD patients. Patients' self-reports and physicians' assessments had a low sensitivity of 27% and 67%, respectively, for detecting regular alcohol intake as indicated by hEtG. CONCLUSIONS: Hair-EtG determination improved the detection of liver transplant patients who used alcohol, and revealed regular alcohol consumption in 32% of ALD and 8% of non-ALD patients.

Determination of ethyl glucuronide in hair improves evaluation of long-term alcohol abstention in liver transplant candidates.

BACKGROUND & AIMS: Prior to listing patients for Orthotopic liver transplantation (OLT) an abstention period of 6 months is required. Ethyl glucuronide in the hair is a new reliable marker for the assessment of alcohol consumption. Here, the diagnostic value of determining the ethyl glucuronide concentration in the hair of liver transplant candidates was evaluated. METHODS: In 63 transplant candidates with alcoholic liver cirrhosis and 25 control patients with cirrhosis of other aetiologies alcohol markers, i.e. hEtG, urine EtG, blood ethanol, methanol and carbohydrate deficient transferrin were determined in parallel to an interview with a psychologist. RESULTS: A total of 19 (30%) transplant candidates admitted alcohol consumption within the last 6 months, while 39/63 (62%) were positive for at least one alcohol marker. In 52% of the 44 candidates denying alcohol consumption, abstention was disproved by detecting at least one positive alcohol marker, in 83% of cases by a positive hEtG result. In the control patients stating abstention from alcohol all hEtG tests were negative. No impact of renal or liver function on hEtG results was detected. A specificity of 98% and a positive predictive value of 92% were calculated for testing hEtG in proximal hair segment and applying a cut-off of 30 pg/mg. CONCLUSIONS: In 52% of patients denying alcohol consumption within the last 6 months, alcohol abstention was disproved, in 83% of cases by hEtG testing. Therefore, hEtG is a promising new marker for the evaluation of long-term alcohol abstention in liver transplant candidates.

Intravenous methadone application as a serious risk factor for an overdose death: methadone-related fatalities in Hamburg from 2007 to 2012.

Methadone plays an increasing role in drug-related deaths in Hamburg. To find out whether intravenous application of methadone plays a relevant role in methadone-related deaths, body fluids of all methadone-positive cases (n=130) and three buprenorphine-positive cases where a urine sample was available (n=58+3) were investigated for disaccharides (sucrose and lactose as markers for intravenous methadone abuse). Sixty-four percent of the urine samples of the methadone cases showed positive results for disaccharides (22 times sucrose alone, range 2 to >1,000 mg/L; 6 times lactose and sucrose; and 9 times lactose alone, range 22 to 382 mg/L). The three buprenorphine cases showed positive results for lactose in urine. In blood, it was not possible to detect any disaccharides. Of the 116 fatal methadone intoxications, 49 % were under opiate maintenance treatment (OMT) at the point of death (A-OMT), 30 % were never in OMT (N-OMT) and 21 % were formerly in an OMT, but not at the point of death (F-OMT). Of the deceased in the OMT group, 12 % (n=7) died within the first 2 weeks of treatment, six of them within the first week. Overall, intravenous abuse of methadone plays a relevant role in methadone-related fatal cases of substituted patients and of drug consumers not in therapy. Thus, it is necessary that therapists keep to the statutory regulations and give take-home doses only after at least 6 months of successful therapy and when there is no suspicion of intravenous abuse.

The undetected murder? Evaluation and validation of a practicable and rapid inductively coupled plasma-mass spectrometry method for the detection of arsenic, lead, and thallium intoxications in postmortem blood.

Homicide, suicide, or accident - elemental intoxication may be a cause in each of these types of deaths. Inductively coupled plasma mass spectrometry (ICP-MS) has emerged as the gold standard analytical method for toxic metal analysis in both clinical and forensic settings. An ICP-MS method was developed using a modified acidic workup for the quantitative determination of arsenic, lead, and thallium. Method validation focused on the assessment of linearity, between- and within-day precisions, limits of detection (LoD) and lower limits of quantification (LLoQ), and carryover. The method was applied to analysis of postmortem peripheral blood samples from 279 forensic cases for which orders for chemical-toxicological examination had been received from the public prosecutor's office. Using six-point and one-point calibrations (latter for rapid screening purposes), precisions and accuracies ranged from -4.8 to 5.8% and -6.4 to 7.5%. Analytical sensitivities for As, Pb, and Tl were 0.08, 0.18, and 0.01 µg/l (LoD) and 0.23, 0.66, and 0.03 µg/l (LLoQ), respectively. Observed postmortem peripheral blood concentrations were As, 1.31 ± 3.42 µg/L; Pb, 17.4 ± 13.1 µg/L; and Tl, 0.11 ± 0.07 µg/L (mean ± standard deviation [SD]). Elemental concentrations, determined in additional quality control samples, were in good agreement to those obtained with an external ICP-MS method based on alkaline sample processing. The current method is practicable and compatible with an ICP-MS system used for trace element analysis in an accredited medical laboratory. It allows for implementation of low-threshold investigations when metal intoxications are suspected in forensic routine.

Quantitative determination of valproic acid in postmortem blood samples--evidence of strong matrix dependency and instability.

Most of the daily work of forensic toxicologists deals with fatal cases resulting from overdoses of licit and illicit drugs. However, another reason for fatalities in patients suffering from epilepsy can be undetectable or subtherapeutic levels of antiepileptic drugs. Some studies have shown a correlation between "sudden unexpected death in epilepsy" (SUDEP) and the ineffective treatment of epilepsy. Low levels of antiepileptic drugs may be a risk factor for SUDEP. The death of a psychiatric patient also suffering from epilepsy inspired the investigation. Subsequent to the death of the patient, the doctor was accused of providing inadequate therapy for epilepsy. The patient was to be treated with valproic acid. We developed and validated a simple method of determining valproic acid levels by gas chromatography-mass spectrometry for serum, but a transfer of the method from serum to postmortem whole blood failed. The method had to be modified and revalidated for postmortem whole blood specimens. A stability study of valproic acid in postmortem blood was conducted, showing a decline of valproic acid levels by 85 % after storage at room temperature for 28 days. During the storage time, the blood samples showed changes in consistency. Depending on the stage of decomposition, it is necessary to perform a determination by standard addition with an equilibration time of 4 h before extraction to achieve reliable results. For a proper interpretation of quantitative results, it is necessary to keep the postmortem decline of valproic acid concentrations in mind.

Analysis of cyclosporin a in hair samples from liver transplanted patients.

INTRODUCTION: Cyclosporin A (CsA) is one of the most important immunosuppressants currently used to prevent organ rejection after liver transplantation. Therapeutic benefit and adverse toxicity are associated with only small differences in CsA blood concentration. Correct individual dosage and compliance are therefore essential for successful therapy. To this end, we developed a validated analytical assay for the determination of CsA in hair samples. Hair samples from patients treated with CsA after liver transplantation were analyzed to investigate correlations between hair concentrations, blood concentrations, and CsA doses. The aim of this study was to evaluate whether hair analysis could be useful for the long-term follow-up of liver transplantation patients. MATERIALS AND METHODS: Hair samples from patients were segmented and decontaminated. After alkaline hydrolysis and liquid-liquid extraction, CsA was analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: The peptide CsA (molecular weight 1202.6 Da) was detected in all the patient hair segments corresponding to times of CsA intake, whereas all hair segments reflecting times without CsA treatment tested negative. Correlation between CsA hair concentrations and CsA doses was poor. Consequently, it was not possible to verify the amount of CsA intake by hair analysis. A correlation coefficient of r = 0.57 was found for the correlation of average whole blood trough concentrations and hair concentrations. The segmental CsA hair concentrations were found to be much steadier than the whole blood trough concentrations. In patients with stable or slightly changed CsA dosages, a comparable segmental concentration profile with a decrease in CsA hair concentrations from proximal to distal was found. Major modifications in CsA dosage are followed by a corresponding trend in segmental hair concentrations. CONCLUSIONS: Our results suggest that it is not possible to quantify the amount of CsA intake by hair analysis. Segmental hair analysis might be useful in the detection of substantial noncompliance and to detect changes in drug-taking behavior.

Methadone and illegal drugs in hair from children with parents in maintenance treatment or suspected for drug abuse in a German community.

BACKGROUND: Children living in homes with drug-addicted parents are in a steady danger of poisoning and may suffer from neglect, maltreatment, and lagging behind in development. Hair analysis could be a suitable way to examine this endangering exposure to drugs. METHODS: Hair samples from 149 children (aged 1-14 years) living with parents substituted by methadone and/or suspected for abuse of illegal drugs, and from 124 of the parents in a German community were investigated by liquid chromatography-hybrid quadrupole time-of flight mass spectrometry and by headspace solid phase microextraction gas chromatography-mass spectrometry for methadone, heroin, cocaine, amphetamines, ecstasy, cannabinoids and benzodiazepines and their metabolites or degradation products (32 compounds). RESULTS: From the children's hair, only in 35 samples, no drugs were detected. Cannabinoids were found in 56 samples, in 20 of them as the only drug. In the remaining 95 samples, methadone was identified 35 times with additional use of illegal drugs in 28 cases. Drug use in the children's environment was obvious for heroin in 44 cases, cocaine in 73 cases, amphetamine or ecstasy in 6 cases, and diazepam in 8 cases. The concentrations varied from limit of quantification to 2.16 ng/mg of methadone, 11.1 ng/mg of 6-acetylmorphine, 17.8 ng/mg of cocaine, 3.29 ng/mg of amphetamine, and 0.72 ng/mg of Δ-tetrahydrocannabinol. In general, hair from younger children contained higher concentrations than from their elder siblings. Systemic incorporation of methadone, cocaine, or cannabinoids appeared likely from detection of the nonhydrolytic metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in 11 cases, norcocaine in 16 cases, and 11-nor-9-carboxy-Δ-tetrahydrocannabinol in 9 cases. Within the families, hair samples of children and parents provided often the same drug pattern. External deposition from smoke and by contact with contaminated surfaces or parent's hands and systemic deposition after passive smoking, administration, or oral intake by hand-to-mouth transfer were discussed as alternative incorporation mechanisms into hair. CONCLUSIONS: Altogether, investigation of children's hair proved to be a useful way to detect endangering drug use in their environment and lead to a more thorough inspection and measures to improve their situation in many of the cases.

Fatal intoxication with 1,4-butanediol: Case report and comprehensive review of the literature.

A fatal case of 1,4-butanediol (1,4-BD) oral ingestion is reported here, in which a 51-year-old man was found dead in his bed. According to the police report, the deceased was a known drug user. A glass bottle labeled (and later confirmed to be) "Butandiol 1,4" (1,4-BD) was found in the kitchen. Furthermore, the deceased's friend stated that he consumed 1,4-BD on a regular basis. The autopsy and histological examination of postmortem parenchymatous organ specimens did not revealed a clear cause of death. Chemical-toxicological investigations revealed gammahydroxybutyrat (GHB) in body fluids and tissues in the following quantities: femoral blood 390 mg/L, heart blood 420 mg/L, cerebrospinal fluid 420 mg/L, vitreous humor 640 mg/L, urine 1600 mg/L, and head hair 26.7 ng/mg. In addition, 1,4-BD was qualitatively detected in the head hair, urine, stomach contents, and the bottle. No other substances, including alcohol, were detected at pharmacologically relevant concentrations. 1,4-BD is known as precursor substance that is converted in vivo into GHB. In the synoptic assessment of toxicological findings, the police investigations and having excluded other causes of death, a lethal GHB-intoxication following ingestion of 1,4-BD, can be assumed in this case. Fatal intoxications with 1,4-BD have seldom been reported due to a very rapid conversion to GHB and, among other things, non-specific symptoms after ingestion. This case report aims to give an overview to the published of fatal 1,4-BD-intoxications and to discuss the problems associated with detection of 1,4-BD in (postmortem) specimens.

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 (