Postmortem Toxicological Analysis Research Articles

B-294 Case report: Postmortem ethanol production following traumatic injury

Abstract Background Ethanol is the most commonly encountered psychoactive substance in forensic toxicology. Accurate interpretation of ethanol concentrations from postmortem samples is fraught with potential hurdles, including decomposition, redistribution, and postmortem production of ethanol. Through the fermentation of substrates like glucose, pyruvate, lactate, and amino acids, microorganisms present in the gut and/or environment can generate ethanol in contaminated human tissues, especially following traumatic injury. The degree of fermentation varies widely depending on the time between death and autopsy, temperature, humidity, tissue glucose concentrations, and the specimen type. Vitreous humor (VH) is the preferred specimen for postmortem toxicological analysis of ethanol because it accurately reflects the antemortem ethanol concentration in serum while being resistant to microbial contamination. This case highlights the utility of VH in an extreme instance of postmortem ethanol production. Methods Postmortem toxicological analysis of liver tissue and VH (NMS Labs, Horsham, PA) was performed by headspace-gas chromatography (HS-GC) Results Case presentation: A man in his sixties with a history of type 1 diabetes mellitus and hypertension was involved in a fatal mining accident while operating heavy machinery in which the equipment fell down a cliff, causing the man to be ejected onto the ground nearby. The decedent was discovered hours after the fall with extensive traumatic injuries to the left side of his body and head. Seven days later, an autopsy was performed by the medical examiner’s office. Postmortem toxicological analysis of liver tissue by HS-GC revealed ethanol at a concentration of 690 mg/100g. The liver tissue also tested positive for amlodipine, nicotine, cotinine, and caffeine. A vitreous humor (VH) sample tested negative (<10 mg/dL) for ethanol. Conclusions The toxicological findings reported herein are inconsistent with antemortem alcohol consumption and are instead an example of severe postmortem ethanol production by microbial contamination. Several factors likely led to the stark discrepancy between the concentrations of ethanol in VH and liver tissue. First, the decedent suffered traumatic injuries, creating conditions favorable for extensive microbial contamination. Second, the time between death and autopsy was seven days, allowing ample time for fermentation to occur, even under refrigerated conditions. Third, postmortem glycogenolysis in addition to the patient’s underlying T1DM likely provided a high concentration of glucose to fuel postmortem fermentation. Ultimately, this case underscores the importance of forensic specimen selection in accurately interpreting toxicology findings following traumatic injury.

Ethanol concentrations in various biological specimens: Living and postmortem forensic toxicology analysis and comprehensive literature review

Alcohol use upsurges the risk for many chronic ill-health consequences such as hepatitis, malignancies, and disastrous outcomes like road traffic accidents ending in fatal injuries. Biochemical and toxicological analysis of different body fluids is crucial for identifying the cause of death and postmortem interval in many forensic cases. Blood, urine, and vitreous fluid are the most valuable body fluids for detecting alcohol during any toxicological analysis. Alcohol is responsible for widespread morbidity and mortality worldwide. Blood alcohol concentration (BAC) is a necessary toxicological test to investigate various crime and accident scenes. This study comprehensively explores the demographic characteristics, BAC distribution, and correlations of alcohol concentrations in postmortem and living cases. Postmortem cases (N = 166) reveal intriguing demographic patterns, with notable variations in year distribution, nationality, sex, age groups, occupation, smoking habits, place of death, and psychiatric history. Living cases (N = 483) exhibit distinct demographic profiles, emphasizing differences in year distribution, nationality, sex, age groups, and smoking habits.Analysis of BAC distribution reveals diverse patterns in both postmortem and living cases, providing valuable insights into the prevalence of different BAC levels in each group. Correlation analyses unveil strong associations between alcohol concentrations in various biological samples in postmortem cases, highlighting the interdependence of blood, vitreous, and urine alcohol concentrations. Conversely, living cases display a moderate positive correlation between blood and urine alcohol concentrations.Comparative analyses showcase significant differences in mean alcohol concentrations between postmortem and living cases, suggesting variations in alcohol metabolism and distribution. These findings underscore the importance of considering temporal factors in interpreting alcohol concentrations in forensic and clinical contexts.In conclusion, this study enhances our understanding of alcohol-related incidents by delineating demographic profiles, BAC distributions, and correlations between different biological samples. Such insights are crucial for refining investigative and clinical approaches, contributing to the broader fields of forensic science and public health.

Loperamide positive deaths in Sweden 2012–2022 and Finland 2017–2022: Fatal loperamide intoxication exclusively for Sweden

Loperamide, a potent μ-opioid receptor agonist used as an antidiarrheal drug, exhibits increased bioavailability at supratherapeutic doses, causing potential central nervous system effects. Its misuse for opioid withdrawal relief and euphoria can lead to dangerously elevated blood levels, causing severe cardiac dysrhythmias and death. This study aimed to compare loperamide positive autopsy cases in Sweden and Finland after the introduction of postmortem toxicological analysis of loperamide, focusing on loperamide’s role in fatalities and identifying common characteristics among those affected. All cases with detected loperamide in femoral blood at forensic autopsies in Sweden (2012–2022) and Finland (2017–2022) were included. In Sweden, loperamide was detected in 126 individuals, and in Finland, in 111 individuals. The incidence of individuals positive for loperamide in postmortem femoral blood increased steadily over the study duration in both Sweden and Finland. Loperamide related fatalities were observed exclusively in Sweden (n=80), predominantly involving younger males with histories of substance abuse, typically classified as accidental deaths. The group of loperamide nonrelated deaths in Sweden mirrored the entirety of cases in Finland. The concentration of loperamide in postmortem femoral blood was significantly higher in cases where loperamide was considered the cause of death (median 0.140 μg/g) compared to cases where loperamide contributed (median 0.080 μg/g), as well as in deaths unrelated to loperamide in both countries (Sweden: median 0.029 μg/g; Finland: median 0.010 μg/ml). The high limit of quantification for loperamide in Sweden may underestimate therapeutic users in epidemiological assessments. This study underscores the absence of loperamide misuse in Finland and indicates a rising trend of loperamide abuse in Sweden.

Review of Heroin Metabolites and Alkaloids Detected in Postmortem Toxicological Analysis

Review of Heroin Metabolites and Alkaloids Detected in Postmortem Toxicological Analysis

Intracranial meningioma: an unusual silent killer—about two cases report and a literature review

BackgroundMeningiomas are common benign intracranial tumors, accounting for 1/3 of all primary intracranial neoplasms, and hence, are not considered the chief cause of death when encountered incidentally during autopsy. These tumors are usually slow-growing, and the clinical course may be asymptomatic to the point of acute complications. Sudden unexpected deaths due to meningiomas are exceptional and rarely reported in the literature.In the present report, we describe two autopsy cases of sudden unexpected death due to meningiomas and we discuss the mechanism of death.Case presentationTwo apparently healthy men were discovered dead in their home. A judicial autopsy was ordered. At dissection, a pedunculated firm mass, attached to the dura was found in both cases. Tumors were located in the anterior and middle fossa. The remaining organs were congestive without any abnormality. A microscopic examination confirmed the diagnosis of meningiomas. Postmortem toxicology analysis was negative. Forensic pathologists concluded to sudden unexpected death due to intracranial meningioma.ConclusionsThese cases illustrate the possibility of meningioma remaining silent till acute complication and fatal outcome. Therefore, clinicians must bear in mind the possibility, albeit extremely rare, of sudden unexpected death in cases of undiagnosed intracranial meningiomas, as documented in the present report. Thus, we emphasize the value of promptly and thoroughly investigating even seemingly minor neurological symptoms, such as headaches or acute epileptic seizures, in adults. We also stress the importance of the early detection and appropriate management of brain tumors in fatal outcome prevention, and we highlight the role of the post-mortem examination to detect such a fatal complication.

B-337 Case Report: Fatal Opioid Overdose Induced by Over-the-Counter Cold Medication Diphenhydramine

Abstract Background Accidental drug-related deaths frequently arise following ingestion of multiple co-intoxicants, including opioid analgesics. Hydrocodone, the most prescribed opioid for pain management, is metabolized by hepatic enzymes CYP2D6 and CYP3A4 to the pharmacologically active metabolite hydromorphone and the inactive metabolite norhydrocodone, respectively. As a result, inhibition of CYP2D6 by other pharmacologic agents can impair the analgesic properties of hydrocodone and prolong its half-life in circulation. One such example is diphenhydramine, which is a potent inhibitor of CYP2D6 activity. This case highlights a drug-drug interaction likely resulting in an accidental fatal opioid overdose. Case Presentation A 58-year-old female had longstanding prescriptions for hydrocodone/acetaminophen (Norco® 10/325), alprazolam, carisoprodol, and diltiazem. The decedent had recently taken an over-the-counter cold medication, diphenhydramine (Benadryl), shortly preceding death. A toxicology report (NMS labs, Horsham, PA) from a post-mortem femoral blood sample detected the presence of the following therapeutic compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 μg/mL), hydrocodone (410 ng/mL), dihydrocodeine (hydrocodol, 24 ng/mL), alprazolam (42 ng/mL), carisoprodol (88 ng/mL), diltiazem (110 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone, the active metabolite of hydrocodone, was not detected (<2 ng/mL). With the exception of hydrocodone, which was present at fatal concentrations, all other compounds were within therapeutic range. Together, these observations are strongly suggestive of a drug-drug interaction leading to impaired hydrocodone metabolism. Conclusions This case report highlights a fatal opioid overdose as a result of CYP2D6 inhibition by diphenhydramine, a readily available over-the-counter medication. Post-mortem toxicological analysis revealed hydrocodone was present in lethal concentrations, whereas its pharmacologically active metabolite, hydromorphone, was undetectable at time of autopsy. Further, the patient was prescribed a formulation of hydrocodone in combination with acetaminophen, which was present at therapeutic concentrations despite the two drugs having similar elimination half-lives. These toxicological findings suggest administration of diphenhydramine precipitated a deadly accumulation of hydrocodone in the deceased. Overall, this case report underscores the importance of understanding and preventing harmful drug-drug interactions in patients taking opioid medications for pain management.

Post-mortem toxicological analysis of cocaine: main biological samples and analytical methods.

This scoping review intends to identify the most used analytical methods and biological samples in the post-mortem forensic toxicological analysis of cocaine and its metabolites. A scoping review was performed based on the question "What are the analytical methods and types of biological samples most frequently used to identify and quantify cocaine in post-mortem forensic toxicology?" The studies were selected from five databases and, after exclusions, the data were tabulated, analyzed, and reported. Twenty-one articles published between 2012 and 2022 were filtered from five different databases to be studied. The collected data indicate that the most used biological samples were blood and hair. The most used sample preparation technique was solid phase extraction, while the most mentioned chromatography method was liquid chromatography with mass spectrometry. This review presents and discusses the state of the art regarding methods for the detection sensitivity spectrum, why limits of quantification are so important for these methods, and what are the most suitable biological samples to be utilized in each case. Cocaine and metabolites are important in forensic toxicologic post-mortem analysis. However, there is little concern in the development of miniaturized and automated sample preparation in this field. Besides, there is not enough understanding of post-mortem redistribution, tolerance, drug-drug interactions, and pre-existing medical conditions.

Fatal concentrations of antidepressant and antipsychotic drugs in post-mortem femoral blood.

Antidepressants and antipsychotics are both an important class of prescription drugs within post-mortem (PM) toxicology because most of the substances are toxic in overdose and the mental disorders being treated may be associated with suicidality. A wide range of antidepressants and antipsychotics are currently included in up-to-date PM toxicology analysis protocols. However, apart from case studies, few reports on fatal concentrations based on large number of cases have been published in the literature. Based on PM investigations in Finland between 2000-2020, this study provides fatal reference concentrations in poisonings due to an antidepressant or an antipsychotic drug assigned as the principal intoxicant. Summary statistics for drug concentrations in PM femoral blood (min, max, mean, 10th, 25th, 50th, 75th, 90thpercentile) were calculated for 17 antidepressant (N = 2007) and for 12 antipsychotic drugs (N = 1161). The proportion of suicide, accident and undetermined manner of death is indicated for each drug. Further, the fatal concentrations obtained in this study were evaluated by comparison with fatal and "normal" PM concentrations reported by two previously published approaches, the grouped causes of death approach and the all causes of death approach, respectively. This study shows that, despite the well-known variation in PM drug concentrations, competently generated fatal concentration results for the drugs studied are consistent to such an extent that they can be used as a reference in the interpretation process.

Oral Cavity Fluid as an Alternative Postmortem Matrix: Comparison to Simultaneously Collected Blood and Urine Specimens.

In postmortem toxicology analysis, a variety of specimens consisting of fluids and tissues are often collected, each with an intrinsic value. Oral cavity fluid (OCF) is emerging as an alternative matrix in forensic toxicology for contributing to a diagnosis in postmortem cases; especially when blood is limited or not available. The aim of this study was to assess the analytical results obtained from OCF and compare them with blood, urine, and other traditional matrices collected from the same postmortem subjects. Of the 62 decedents studied (including 1 stillborn, 1 charred, and 3 decomposed subjects), 56 had quantifiable drugs and metabolites data in the OCF, blood, and urine. Notable findings were benzoylecgonine (24 cases), ethyl sulfate (23 cases), acetaminophen (21 cases), morphine (21 cases), naloxone (21 cases), gabapentin (20 cases), fentanyl (17 cases), and 6-acetylmorphine (15 cases), which were detected more frequently in OCF than in blood (heart, femoral, or body cavity) or urine. This study suggests that OCF is a suitable matrix for detecting and quantifying analytes in postmortem subjects compared with traditional matrices, particularly when other matrices are limited or difficult to collect because of body condition or putrefaction.

Burnt to blazes: homicidal act of strangulation with post mortem burn: A case report

In India, nearly 1 million people got the injury by burn in which 10 percent cases occurs accidentally ¹. Post mortem burned body has always been a difficult and challenging task for forensic investigations. This case report consist of homicide involving post mortem burns with aim to abolish the identity and cover up the cause of death of the corpse. The aim of study is to establish the identity in relation to age, sex, time, cause and manner of death in burn corpses by postmortem examination. Body was found burning at the abandoned place absence of vitality signs are factors indicative of postmortem burning following homicide. Post Mortem examination with careful interpretation of all evidences includes clothes, bones and other exhibits found at the crime scene along with postmortem radiography and toxicological analysis can play a key role in every such cases.

Poisons and Drugs Used in Homicidal Poisoning: A Systematic Review

Homicidal poisoning defined as the application of toxic agents by a person to kill human beings. Historically, some conventional homicidal poisons were including arsenic, cyanide, mercury, strychnine, aconite and atropine. In general, homicidal poisonings are among the least frequently detected crimes and difficult to establish, across the world. Lack of suspicion of this type of poisoning and clinical presentations in this poisoning are often misdiagnosed as natural disease, especially if the crime is occurred in a hospital setting are the limitations for detection of homicidal poisonings. The aim of this article is to review of drugs and poisons used in recently reported homicidal poisoning cases. The results showed that the contemporary poisons and drugs used in homicidal poisonings are based in combinations of old and well-described poisons and drugs and natural or synthetic drugs and poisons from the group of organophosphorus agents, tetrodotoxin, radioactive substances and polydrug pattern of antipsychotics with antidepressants and sedativehypnotics. Forensic autopsy and postmortem histopathological and toxicological analysis have a critical role in investigation on homicidal poisoning fatal cases. The sophisticated instrumental analysis (usually using tandem mass spectrometry) can be used for toxicological analysis of trace levels of drugs and poisons in routine and alternative samples in the victims of homicidal poisoning.

Reported mortality of Griffon VultureGyps fulvusin central Italy and indications for conservation and management

SummaryVultures are long-lived species sensitive to human-caused mortality that has already determined a widespread collapse in Asian and African populations. They provide significant ecosystem services (regulatory and cultural) consuming livestock carcasses and saving greenhouse gas emissions, favouring nutrient recycling, environmental sanitation, and providing financial revenue. Appraising the incidence and causes of mortality could help to improve management and conservation actions. We compiled records of reported mortalities for the reintroduced Griffon VultureGyps fulvuspopulation of the central Apennines in Italy (123 cases, July 1994–December 2020). The average mortality was 4.69 vultures per year (± 1.14 SE), with no significant temporal trend. The peak of mortality events, estimated by harmonic regression analysis, was in March, while the minimum occurred in October. No differences were found among age classes and sex ratio mortality was established at 1.43:1 (M:F,N= 68). Out of 103 (83.7%) vultures which underwent a post-mortem and toxicological screening, 53% were poisoned, mainly by carbamates, and 27% died of unknown causes. Overall, direct or indirect anthropogenic mortality caused 67% of deaths. Even considering an inherent bias associated with reported mortality as to the prevalence of causes of death and estimation of mortality rates, the overwhelming relevance of poisoning highlights that existing anti-poisoning efforts should be refined and incorporated into a coordinated multidisciplinary strategy. A standardised approach, from vulture carcass discovery to post-mortem procedures and toxicological analysis, should be applied to reduce uncertainty in the determination of causes of death, increasing effectiveness in the prosecution of wildlife crimes. As most of the poisoning cases affecting the Griffon Vulture population in the central Apennines likely represent a side (though illegal) effect of retaliatory efforts to defeat livestock predators, effective strategies in reducing human–wildlife conflicts should be applied.

Bioanalytical method for simultaneous determination of benzodiazepines in vitreous humor using liquid chromatography-tandem mass spectrometry

The use of vitreous humor (VH) in forensic casework has been growing in the last years due to numerous advantages. Several compounds can be evaluated in this matrix, including benzodiazepines whose determination is essential due to their great availability and potential of dependance and misuse. Postmortem toxicological analyses are required to determine the influence of benzodiazepines in deaths. However, most of the analytical methods which determine these drugs in VH are laborious and time consuming. This article describes a simple method based on protein precipitation for the determination of eight benzodiazepines in VH samples. Samples were prepared through a protein precipitation method and analyzed by liquid chromatography tandem mass spectrometry. Solvent choice and sample and solvent volumes for precipitation were optimized using chemometric approaches. The method was validated for selectivity, lower limit of quantification (LLOQ), linearity, carryover, precision, bias, matrix effect and dilution integrity. In order to verify the applicability, 62 vitreous humor samples were analyzed. LLOQs were 1 ng/mL and calibration curves were linear from 1 to 25 ng/mL (r2 > 0,99) for all analytes. Bias, precision and dilution integrity results were satisfactory according to proper guidelines. Ionization suppression was significant with values ranging from 8 to 37%. Two samples from real cases were positive for diazepam with the following concentrations: 6.80 ng/mL and 47.68 ng/mL, approximately 10 times lower than those found in peripheral blood. The procedure described here can be used as a straightforward and low cost method for the quantitation of multiple benzodiazepines in VH.

Utilization of Brain Tissue as A Viable Postmortem Toxicological Specimen: A Review on Collection and Preservationof Samplefor Toxicological Analysis and Its Advantage Over Other Specimens

Collection of proper autopsy specimen and preservation are essential stepsfor the toxicological analysis in Forensic Medicine. Faulty collection and preservation of the specimens/samples can greatly alter or negate forensic chemical or toxicologicalexamination. In forensic toxicology practicein Bangladesh, postmortem specimen that is subjected to toxicological examinations generally focusing on mainly blood and sometimes urine or other fuds from different body cavities. Analysis of blood from different anatomical sites and tissue samples and urine may assist in the interpretation of the postmortem results. However, in many postmortem cases, there is little or no blood for quantitative drug analysis, or there might be such traumatic injury which led to significant blood loss or there is possibility of contamination form contents of the ruptured stomach. Besides, analysis of urine reveals negative result, if death occurs closely the time of intoxication. Given the circumstances, brain tissue may be a valuable specimen in postmortem toxicological analysis. The position of the brain in the body secures a tremendous protection and isolation which can eliminates or at least attenuates many of the interpretive challenges with postmortem blood, urine or other fluid specimens.This review paper is an update on the standard methods of brain tissue specimen collection and preservationprocedures for toxicological analysis and its value as well as advantages over other specimens, which might be of possible interest for forensic professionals in the country. Bang. J Neurosurgery 2022; 11(2): 114-117

An unusual case of fatal hypothermia involving topical diphenhydramine.

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. 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. 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 0.44μg/mL in blood and 2500μg/mL in urine. 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.

Validation of gas chromatography mass spectrometry (GC-MS) qualitative method for detection of paraquat in postmortem samples by sodium borohydride-platinum chloride chemical reduction

To develop a GC-MS method for the detection of paraquat by sodium borohydride-platinum chloride reduction in postmortem samples. Paraquat [1,1′-dimethyl-4,4′-bipyridilium dichloride,(PQ)] is a bipyridylium quaternary ammonium contact herbicide. At the Institute of Forensic Science and Legal Medicine (IFSLM), an average of 13 cases of PQ poisoning are submitted annually for postmortem toxicological analysis. Previously a colorimetric method for the identification of PQ was used. A more sensitive method was needed to confirm the presence of PQ. There is limited studies on liquid-liquid extraction (LLE) of postmortem fluids and tissues for determination of PQ by GC-MS. Some methods used a chemical reduction involving sodium borohydride (NaBH4) or sodium borohydride with nickel chloride (NaBH4-NiCl2), prior to LLE, to gain more volatile compounds for analysis. In the absence of NiCl2, platinum (IV) chloride (PtCl4) was used as a substitute catalyst in the validation. The aim of this validation is to identify PQ in suspected poisoning cases from postmortem samples using chemical reduction reaction, followed by LLE and then (GC-MS). The qualitative method involved an initial chemical reduction of PQ to the perhydrogenated product and monoene by-product: 500 μL blood, urine or tissue homogenate was placed in a glass tube, followed by 200 μL toluene, 400 μL PtCl4 (1% w/v) and then 500 μL NaBH4 (40% w/v) was added dropwise. The mixture was vortexed then left to stand for 1½ hours at room temperature. 1 mL 5 N sodium hydroxide solution was added to stop the reaction. For LLE, 3 mL hexane: ethyl acetate (4:1) was added to the tube and placed on shaker for 45 minutes at 300 rpm. The sample was centrifuged for 1 hour at 1400 g. The hexane:ethyl acetate layer was then transferred to a beaker and allowed to evaporate to dryness. The residue was reconstituted with 1 mL hexane, transferred to GC vial, and allowed to evaporate to dryness. The residue was then reconstituted with 100 μL hexane, and transferred to a GC vial fitted with glass insert, with 1 μL being injected into the GC-MS system (Agilent 7890A GC coupled with an Agilent 5975C VL MSD with Triple Axis Detector Mass Spectrometer). As recommended by the Scientific Working Group for Forensic Toxicology (SWGTOX), the validation parameters for qualitative confirmation/identification were specificity, recovery, carryover, repeatability and limit of detection. The method was applied to blank blood and urine samples, spiked blood and urine samples, as well as 10 suspected PQ poisoning cases (24 postmortem samples) submitted to the IFSLM. The blank blood and urine samples analysed did not yield any positive results for the analytes of interest. Blood and urine samples spiked with the PQ standard solution resulted in the detection of both the perhydrogenated product and monoene by-product. The limit of detection for both reduction products was 30 ppm. There was no detection of the analytes in the three blanks analysed after an injection of 1000 ppm PQ. The reduction products of PQ were detected in all 10 cases. Four of these cases had previously given negative results using the colorimetric test. The PtCl4 was found to be an adequate substitute catalyst in the reduction procedure. The procedure was proven to be sensitive, repeatable and robust. All sample types assessed by the method gave positive results, however stomach and content produced the best chromatograms with sharp, clearly defined and resolved peaks. In summary, the presented procedure provided excellent performance in the identification of the reduction products of PQ in postmortem samples.

Review of findings in a case series of NPS benzodiazepines in UK deaths

Review the other drugs present and circumstances in fatalities where NPS benzodiazepines have been detected in a case series from the UK. Determine the most frequent NPS benzodiazepines involved in deaths and concentrations where possible. Benzodiazepine-type New Psychoactive Substances (NPS) have been increasingly detected in toxicology casework worldwide. These NPS benzodiazepines are potentially more potent than traditional benzodiazepines and may present an increased risk to the user, especially if other CNS depressant drugs are taken. Also, concentration data are sometimes lacking that may be useful in determining additional toxicological significance to the cause of death. As part of routine post-mortem toxicology analysis, NPS benzodiazepines have been detected, and where able, measured in blood by LC-MS-MS. Data from 35 cases involving such drugs are presented, including other drug and alcohol findings as well as the context of the death (e.g. drug related death or alternative cause). The number and frequency of different NPS benzodiazepines has been compiled along with concentrations (where available) as well as other drug findings collated by drug type. Across the 35 fatalities, 7 different NPS benzodiazepines were detected. In decreasing order of frequency; flubromazolam (13 cases), bromazolam (12), etizolam (9), flualprazolam (5), flubromazepam (1), phenazepam (1) and bromazepam (1). 80% of cases had only one NPS benzodiazepine present with 20% of cases having two NPS benzodiazepines. All fatalities were either a drug related death–83% (including cases where other drugs were present that may have been more significant than the NPS benzodiazepines) or involved an alternative cause of death–17% (including hanging, hit by a train or other medical cause). Other drugs or alcohol were detected in all cases; traditional benzodiazepines (e.g. diazepam, lorazepam, clonazepam, alprazolam) were the most common (28 detections), followed by cocaine and antidepressants (21), methadone (16), heroin/morphine (15), pregabalin (14), codeine (12), other opioids (12), alcohol and cannabis (8), zopiclone (5), ibuprofen/paracetamol (4), ketamine, antipsychotics and anticonvulsants (3), antihistamines, amphetamines and erectile dysfunction drugs (2). In terms of concentrations (where measured), flualprazolam concentrations ranged 8.7-26 ng/mL (median 20 ng/mL, n = 5), flubromazolam concentrations ranged 2.9-45 ng/mL (median 13 ng/mL, n = 11) and etizolam concentrations ranged 4.6-95 ng/mL (median 37.5 ng/mL, n = 6). As drugs with CNS depressant capabilities, NPS benzodiazepines present a risk of toxicity to users, especially if other CNS depressant drugs are co-used. This risk is increased due to the availability of these drugs often as adulterants or in falsified traditional benzodiazepines (such as diazepam and alprazolam), whereby the user may not be aware of the constituent drugs in any product consumed and this was suspected to have occurred in some of the cases featured along with use of traditional benzodiazepines as well. The review shows that poly-drug use is a particular issue with these cases; principally traditional benzodiazepines, cocaine, heroin/morphine, antidepressants, methadone and other opiates and opioids. The concentrations of NPS benzodiazepines found, where measured, provide some data for toxicologists if investigating post-mortem casework and indicate a need for sensitive qualitative and quantitative techniques. The concentrations also overlap with available data for other (non-fatal) case types such as driving under the influence so “fatal” ranges do not seem to apply. NPS benzodiazepines have been detected in a number of drug related and non-drug related deaths in the UK supporting their prevalence worldwide. Toxicologists should ensure the necessary analytical capabilities to detect what could be low concentrations despite presenting potential toxicological significance to cause of death.

Simultaneous fatal poisoning of two victims with 4F-MDMB-BINACA and ethanol

PurposeMethyl-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.MethodsThe 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).ResultsThe 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.ConclusionAccording 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.

Morphine Accumulates in the Retina Following Chronic Systemic Administration.

Opioid transport into the central nervous system is crucial for the analgesic efficacy of opioid drugs. Thus, the pharmacokinetics of opioid analgesics such as morphine have been extensively studied in systemic circulation and the brain. While opioid metabolites are routinely detected in the vitreous fluid of the eye during postmortem toxicological analyses, the pharmacokinetics of morphine within the retina of the eye remains largely unexplored. In this study, we measured morphine in mouse retina following systemic exposure. We showed that morphine deposits and persists in the retina long after levels have dropped in the serum. Moreover, we found that morphine concentrations (ng/mg tissue) in the retina exceeded brain morphine concentrations at all time points tested. Perhaps most intriguingly, these data indicate that following chronic systemic exposure, morphine accumulates in the retina, but not in the brain or serum. These results suggest that morphine can accumulate in the retina following chronic use, which could contribute to the deleterious effects of chronic opioid use on both image-forming and non-image-forming visual functions.

Evaluation of forensic autopsy cases with substance use detected in Izmir, Turkey

Using postmortem toxicological analyses, we aimed to determine the origin and cause of death and type of substance used in substance use-related deaths. A total of 7475 autopsies were performed between January 2015 and December 2017 in İzmir, Turkey. In our retrospective analysis, substance use was detected in 449 (6.0%) autopsies. The majority (96.4%) were male. The most frequent deaths (18.5%) occurred in the 25–29 age group. Of the 55.2% of the cases that died of unnatural causes, accident-related events (22.9%) were most frequent. Trauma/injury caused death in 37.0% of cases and substance intoxication in 24.7%. Cannabis use was detected in 34.3% of the samples, and multiple substance use in 25.4%. Accordingly, It is thought that a multidisciplinary approach can be successful in preventing substance use and related problems.