Systematic Toxicological Analysis Research Articles

Enhanced autopsy triage (EA-Triage) in drug-related deaths: integrating quick toxicological analysis and postmortem computed tomography.

The objective was to assess the diagnostic accuracy of an enhanced autopsy triage (EA-Triage) setup consisting of postmortem computed tomography (PMCT), simulated quick toxicological analysis (sQTA), external examination, and case information in determining cause of death (COD) in persons with past or current use of illegal drugs (drug-related deaths). Information on drug-related deaths selected for medico-legal autopsy in 2020-2021 at the Department of Forensic Medicine, Aarhus University, Denmark, was analyzed retrospectively. The included cases underwent conventional autopsy, PMCT, and systematic toxicological analysis. A board-certified forensic pathologist, who was blinded to the internal examination and COD from the medico-legal autopsy, determined COD based on the EA-Triage setup. 154 cases with a median age of 40.6 years (range 17-70 years, 82% males) were included. The COD determined by medico-legal autopsy and that determined by EA-Triage matched in 113 cases (73%), including those with an unknown COD. EA-Triage and medico-legal autopsy determined unknown COD in 45 (29%) and 5 cases (3%), respectively. Excluding cases with an unknown COD, EA-Triage predicted COD in 109 cases (71%); of those, 72 (66%) had no unexplained case circumstances or suspicion of a criminal act. In these 72 cases, the CODs determined by EA-Triage and medico-legal autopsy matched in 71 cases (99%), and the sensitivity and specificity for detecting lethal intoxication were 100% and 90%, respectively. EA-Triage showed strong diagnostic accuracy for determining COD in drug-related deaths. This method may be suitable for enhancing preautopsy triage and guiding police investigations at an early stage.

Automated enzymatic hydrolysis of urine samples for improved systematic toxicological analysis of drug-facilitated sexual assault cases.

Drug-facilitated sexual assault (DFSA) is characterized by victim incapacitation due to intoxicating substances. Detection of single drug exposure from DFSA requires a systematic toxicological analysis strategy including sensitive methods covering a broad spectrum of substances. The aim of this study was to develop and validate an UHPLC-MS/MS screening method for analysis of samples from DFSA cases and incorporate an automated enzymatic pre-treatment of urine samples into a robotic sample preparation for an efficient laboratory workflow. The screening method included 144 drugs of abuse, pharmaceuticals, and metabolites relevant to DFSA. The use of a recombinant enzyme showed an efficient glucuronide hydrolysis with an average parent drug recovery of 97%. Investigation of matrix effect showed no pronounced ion enhancement or suppression for most analytes (96%), and extraction recovery was above 80% for 97% of analytes. Process efficiency ranged from 50% to 138% for most analytes. The LODs ranged from 0.0001 mg/L to 2 mg/L depending on analyte, and most analytes met the SOFT recommended minimum performance limits. The validated method was applied to authentic suspected DFSA cases (n = 38). Results showed that drugs of abuse, benzodiazepines, and antidepressants were most commonly found in suspected DFSA cases. Incorporation of an automated enzymatic hydrolysis step during sample preparation enables a fast and simple workflow for simultaneous analysis of blood and urine samples for an improved systematic toxicological analysis strategy for DFSA cases.

A fatal case of aspiration due to consumption of the hallucinogenic tryptamine derivative dipropyltryptamine (DPT)

Background and aimThis case involves a 20-year-old man with prior hallucinogen-use experience, who sniffed an unknown amount of dipropyltryptamine in an apartment. Dipropyltryptamine, a hallucinogenic compound belonging to the tryptamine class is recognized for inducing effects similar to dimethyltryptamine (DMT) but with a longer duration. Ten to fifteen minutes later he experienced visual hallucinations, followed by increasing apathy. Two hours post consumption he developed abdominal pain, leading to collapse, seizure, and vomiting. Despite emergency medical resuscitation on site, transport to hospital 2.5 hours post consumption and extracorporeal life support he died 21 hours later. Relevant toxicological and morphological findings are presented. MethodsA serum sample was collected four hours post consumption. Autopsy was performed six days after death. Antemortem serum, as well as postmortem cardiac blood and urine were analyzed for alcohol and psychoactive drugs by systematic toxicological analyses employing gas chromatography-mass spectrometry (Maurer/Pfleger/Weber library among others), liquid chromatography-ion trap mass spectrometry (LC-MSn, Toxtyper™), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Dipropyltryptamine was quantified by LC-MS/MS after solid-phase extraction. ResultsAutopsy revealed a state after deep aspiration of gastric contents with consecutive brain edema due to oxygen deprivation. Dipropyltryptamine concentrations were approximately 210 ng/ml, 110 ng/ml and 180 ng/ml in antemortem serum, postmortem cardiac blood and urine, respectively. To the best of our knowledge, these are the first reported concentrations of dipropyltryptamine in a fatal case. ConclusionUnlike typical tryptamine overdose reports, this case did not present with agitation, hyperthermia, or tachycardia. Despite the individual's prior experience with tryptamines and the generally low toxicity associated with this class of hallucinogens, death in this case was an indirect consequence of the nasal consumption of a high dose of dipropyltryptamine.

Drug‐facilitated sexual assault in Africa: A scoping review of empirical evidence

AbstractBackgroundSexual assault has been a major social problem worldwide. Drug‐facilitated sexual assault (DFSA) is a form of sexual assault facilitated by psychoactive substances. DFSA is highly prevalent worldwide, though it is usually underreported. To understand the situation of DFSA in Africa, there is a need to map the available empirical evidence on DFSA in Africa. Hence, this scoping review was conducted to summarize the existing empirical knowledge and gaps in the literature and inform future research on DFSA in Africa.MethodsThis study adopted the design by the Arksey and O'Malley's guideline for scoping reviews. Without year limiters, literatures were retrieved through a systematic search of the 11 electronic databases using appropriate search terms and Boolean operators. The retrieved literatures were deduplicated and screened, using Rayyan, to identify eligible literature for inclusion into the review. Only those articles that met the eligibility criteria were included for data charting, collation, and summarization. Four articles were included in this review.ResultsFour articles were included in this review. The studies reported the characteristics of offenders and the context in which DFSA occurred. In the reviewed studies, rape of men was only reported among South Africans. Sedatives and alcohol are the most reported substances used in such rape. Perceptions of date rape, as documented by sexual assault survivors, suggest the pervasiveness of victim blaming. Typical DFSA cases appear opportunistic in nature, and an acquaintance is often the culprit. However, disaggregating DFSA as a specific sexual assault requires some logistics, including forensic and toxicological investigations.ConclusionDFSA is a significant dimension of gender‐based sexual violence. Infrastructure development should be improved to support systematic toxicological analyses and services to investigate and understand DFSA.

E-Cigarette Toxicology and Public Health — Exploring the Safety of E-Cigarette Compared to Traditional Cigarette

With the popularity of e-cigarettes, there are concerns about the potential health risks associated with inhaling e-cigarette aerosols, which contain a complex mixture of chemicals including nicotine, flavourings and poisons. This paper presents a systematic toxicological analysis of several chemicals commonly found in e-cigarettes. The chemical properties and toxicity of nicotine, propylene glycol, vegetable glycerin, benzaldehyde and cinnamaldehyde are discussed in relation to their use in e-cigarettes, with an emphasis on the hidden health risks involved. Nicotine is a highly addictive alkaloid that causes oxidative stress, neuronal apoptosis, DNA damage, and is highly toxic. E-cigarette solvents, such as vegetable glycerine and propylene glycol, can activate melanin production in the skin and raise the likelihood respiratory infections. Flavouring agents like benzaldehyde and cinnamaldehyde can induce cellular damage and heighten the susceptibility to disease like cancer and cardiovascular disease, particularly in individuals with specific genetic variants of the ALDH2 enzyme. The discussion revealed a lack of research to fully understand and assess prolonged health effects of e-cigarette use. However, both clinical and marketing should highlight the known possible risks. Clinicians should advise patients accordingly, and regulators must closely monitor the sale and promotion of e-cigarettes and be transparent about any potential harms to safeguard the welfare of consumers.

Overview of systematic toxicological analysis strategies and their coverage of substances in forensic toxicology.

Systematic toxicological analysis (STA) is the process of using an adequate analytical methodology to detect and identify as many potentially toxicologically relevant compounds as possible in biological samples. STA is an important part of everyday routine work within forensic toxicology, and several methods for STA have frequently been published and reviewed independently. However, the many drugs and other substances involved, as well as the constant emergence of new ones, may pose a major challenge in STA, which often demands a strategy involving multiple analytical methods in parallel. Such strategies have been published and evaluated less frequently despite their relevance in forensic toxicology. This mini-review briefly summarizes commonly applied methods for STA in forensic toxicology, including gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-MS (LC-MS) methods, and highlights some of their potential pitfalls. Second, it provides an overview of previously reported strategies to conduct STA, including a presentation of the STA strategy applied in the authors' laboratory. This involves broad drug screening by LC-high-resolution MS, supported by targeted screening and quantification using LC-tandem MS, headspace (HS)-GC-MS, HS-GC-flame ionization detector and other complementary methods. The STA strategy aims to cover as many potentially relevant drugs as possible and seeks to reduce potential pitfalls arising in forensic casework. The review underlines that not every substance can be identified in all circumstances even with a comprehensive STA strategy.

Systematic toxicological analysis of the effect of salinity on the physiological stress induced by triphenyltin in Nile tilapia

Triphenyltin (TPT), a synthetic chemical, is prevalent in complex salinity areas, including estuaries and coastal regions. However, current studies on the toxicological effects of TPT relevant to the environment at different salinities are limited. In the study, biochemical, histological, and transcriptional analyses of TPT and salinity alone, or in combination, was performed on the Nile tilapia (Oreochromis niloticus) liver. Nile tilapia exhibited weakened antioxidant defenses and liver damage. Transcriptomic analysis revealed that TPT exposure primarily affected lipid metabolism and immunity; salinity exposure alone particularly affected carbohydrate metabolism; combined exposure primarily immune- and metabolic-related signaling pathways. In addition, the single exposure to TPT or salinity induced inflammatory responses by up-regulating the expression of pro-inflammatory cytokines, whereas combined exposure suppressed inflammation by down-regulating pro-inflammatory cytokine levels. These findings are beneficial to understand the negative effects of TPT exposure in Nile tilapia in the broad salinity zones and its potential defense mechanisms.

Thin Layer Chromatographic Method for Detection of Conventional Drug Adulterants in Herbal Products

Commercially available conventional drugs have been used to adulterate herbal products. Considering the rapid growth of herbal products’ market, it is essential to screen herbal products for the presence of conventional drugs. Simple analytical methods are needed for the rapid screening of conventional drugs that are likely to be adulterated in herbal products. Thin layer chromatography (TLC) methods for screening twelve conventional drugs in herbal products have been developed and applied. The analytes were extracted from herbal products using acetonitrile:methanol:acetic acid:water (4:4:1:1, v/v). Solvent mixture of dichloromethane:ethyl acetate:methanol (75:15:10, v/v) separated well trimethoprim, sildenafil, paracetamol, and sulfamethoxazole while pyrimethamine, metronidazole, and sulfadoxine were well separated by dichloromethane:ethyl acetate:methanol (77.5:12.5:10, v/v). In addition, acetyl salicylic acid, ibuprofen, diclofenac, quinine, and lumefantrine were well separated by ethyl acetate:methanol:30% ammonia (75:22.5:2.5, v/v). Chromatographic separations were found to be highly reproducible, and more than 10 samples can be analysed in one run. The method was applied in the screening of 229 herbal products. Consequently, 24.0% of the samples contained one adulterant, while 21.4% contained at least two adulterants. All conventional drugs detected in herbal products were not mentioned on the labels and therefore the consumers are kept unaware of their side effects and health problems. Further studies for confirming and quantitatively determining the adulterants in a wide range of products as well as a systematic toxicological analysis of the adulterants in herbal products are recommended.

Clinical Toxicological Follow-Up Analysis of a Suicide Attempt Using Chloroquine.

Chloroquine, a drug approved for the treatment of malaria, is frequently used to commit suicide. We report about a suicide attempt by ingesting a high dose of chloroquine in combination with other drugs. Findings of the emergency toxicology screening of blood and urine and those of the follow-up analyses in blood are discussed. Systematic toxicological analysis approaches revealed the presence of chloroquine, butylscopolamine, cafedrine, diazepam, lorazepam, metoclopramide, nordazepam, norephedrine and 11-nor-9-carboxy-∆9-tetrahydroxycannabinol in blood and/or urine of the subject. Suicide due to a combination of chloroquine and benzodiazepines is known as the so-called "Kusch method" in German-speaking countries. The initial chloroquine plasma concentration was determined to be 9.6 mg/L after precipitation and analysis by liquid chromatography-high-resolution tandem mass spectrometry. The analytical procedure was developed ad hoc and validated in accordance with international recommendations. Clinical toxicological follow-up analyses in blood were performed over a period of 3 weeks. The chloroquine concentration remained above the therapeutic range (up to 0.5 mg/L) for 2 weeks and dropped to 0.3 mg/L after 3 weeks. Furthermore, monodesethylchloroquine (MDCQ) and bisdesethylchloroquine (BDCQ) were determined to be the most abundant metabolites in plasma. Within 3 weeks, the area ratios of MDCQ and chloroquine increased 4-fold (from 0.090 to 0.350), and those of BDCQ and chloroquine increased 100-fold (from 0.002 to 0.218). This information may help to estimate the chloroquine excretion progress in the future.

Poisoning with atropine-based eye drops: An almost perfect murder?

A 56-year-old man was found unresponsive in his bathroom by his daughter, and declared dead by the mobile emergency and resuscitation service (SMUR). There were no signs of tampering or an intervention by a third party. However, in the absence of the deceased's wallet and identification documents, the emergency doctor cannot certify the death as natural. Thus, the Public Prosecutor's Office launched an investigation and a forensic doctor was required at the scene. The man was known to be an alcohol addict and numerous licit drugs were prescribed. The deceased had a new friend since 6 months. An external examination and an autopsy were done by a forensic pathologist. A systematic toxicological analysis (STA) was performed on blood, urine and gastric content. In addition, other investigations such as financial data, mobile phone transcripts, etc. were initiated. A rectal temperature of 41.2 °C, bilateral mydriasis and the absence of traumatic lesions was observed during the external examination of the body. The autopsy revealed hepatic steatosis, chronic dilated cardiomyopathy, acute pulmonary edema and a vesical globe. STA was positive for alcohol, alprazolam, venlafaxine, bisoprolol and atropine. Despite a therapeutic atropine blood concentration (23 ng/mL), this compound turns out to be the main element of this case. With its short half-life, atropine intoxication cannot be excluded, certainly in the event that a significant period of time has elapsed between the intake of atropine and death. Dose estimates of consumed atropine were made on the basis of the STA urinary concentration and the volume of urine in the bladder noted during the autopsy. Depending on the route of administration, the dose of atropine consumed would be at least 20 times higher than in a therapeutic setting. Research concerning the new friend of the deceased revealed some interesting findings: (a) a search of medical prescriptions of the friend revealed two prescriptions for Isopto-Atropine®, the day before or the day of death, delivered in two different pharmacies, (b) a third prescription was dispensed four months earlier, (c) the mobile phone transcripts raised suspicion of another poisoning. This person was hospitalized but fully recovered. The urine sample collected at the hospital of this third person was sent for STA. This sample revealed the presence of four drugs identical to those identified in the deceased, namely alprazolam, venlafaxine, bisoprolol and atropine. After a consistent denial of committing a crime on the second day of the trial, the accused admitted having emptied two bottles of Isopto-Atropine® into the beer of the deceased victim. This confirmed what we had calculated as dose.

Liquid Chromatography High-Resolution Mass Spectrometry in Forensic Toxicology: What are the Specifics of Method Development, Validation and Quality Assurance for Comprehensive Screening Approaches?

The use of high-resolution mass spectrometry (HRMS) has increased over the past decade in clinical and forensic toxicology, especially for comprehensive screening approaches. Despite this, few guidelines in this field have specifically addressed HRMS issues concerning compound identification, validation, measurement uncertainty and quality assurance. To fully implement this technique, certainly in an era in which the quality demands for laboratories are ever-increasing due to various norms (e.g. the International Organization for Standardization's ISO 17025), these specific issues need to be addressed. This manuscript reviews 26 HRMSbased methods for qualitative systematic toxicological analysis (STA) published between 2011 and 2021. Key analytical data such as samples matrices, analytical platforms, numbers of analytes and employed mass spectral reference databases/libraries as well as the studied validation parameters are summarized and discussed. The article further includes a critical review of targeted and untargeted data acquisition approaches, available HRMS reference databases and libraries as well as current guidelines for HRMS data interpretation with a particular focus on identification criteria. Moreover, it provides an overview on current recommendations for the validation and determination of measurement uncertainty of qualitative methods. Finally, the article aims to put forward suggestions for method development, compound identification, validation experiments to be performed, and adequate determination of measurement uncertainty for this type of wide-range qualitative HRMSbased methods.

Detection of atomoxetine and its metabolites in the urine by thin-layer chromatography and mass spectrometry

The aim of the study was the detection of atomoxetine and its biotransformation products in the urine under TLC screening conditions and identification of the metabolites using mass spectrometry method. Materials and methods. The volunteer’s urine samples after taking a single therapeutic dose of atomoxetine (2 capsules of 60 mg each of Strattera®) were studied. Sample preparation included diluting acid hydrolysis followed by the native compound and metabolites extraction with chloroform from the saturated solution of ammonium sulfate at pH of 11–12. Thin-layer chromatography studies of the extracts were carried out in 18 mobile phases including those proposed by The International Association of Forensic Toxicologists for general drug screening, and those widely used in forensic toxicological studies. The color reactions were carried out using a range of chromogenic reagents. A Varian 1200 L mass spectrometer (Netherlands) equipped with a dual quadrupole mass analyzer was applied for analysis of the eluates from chromatograms. Identification was undertaken at the direct introduction of the sample into the ion chamber, electron-impact ionization (70 eV), and full ion scanning mode. Results. The spot of the native drug on the chromatogram was identified by the Rf, value. Two atomoxetine biotransformation products were identified by the molecular weights that correspond to the molecular ion peaks in the mass spectra. Conclusions. Atomoxetine and its biotransformation products were detected in the urine under TLC screening conditions and identified using mass spectrometry method. Chromatographic mobility of the native compound, hydroxyatomoxetine, and dihydroxyatomoxetine in the TLC screening systems as well as the results of their visualization using chromogenic reagents applied for toxicological drug screening in the systematic toxicological analysis have been determined.

Metabolomics-driven determination of targets for salicylic acid and ibuprofen in positive electrospray ionization using LC-HRMS.

Due to the large number of basic therapeutic and illicit drugs, systematic toxicological analysis has widely been performed with liquid chromatography coupled to mass spectrometry using positive electrospray ionization. However, there exist a smaller number of drugs, typically acidic drugs, which require the use of negative electrospray ionization either via a separate analysis or polarity switching. Here, targets relating to salicylic acid and ibuprofen in positive electrospray ionization were determined through a metabolomics-driven retrospective investigation of forensic casework. Samples were previously screened using liquid chromatography coupled with high-resolution mass spectrometry with quantification of target analytes performed using liquid chromatography with tandem mass spectrometry. Of the 1,717 whole-blood samples submitted between 2014 and 2019, 48 were positive for salicylic acid (1.1-1,400 mg/kg) and 78 for ibuprofen (1-46 mg/kg). Based on the retrospective analysis, 19 and 90 targets were identified for salicylic acid and ibuprofen, respectively. For targets of salicylic acid, the protonated adduct of salicyluric acid ([M + H]+ , m/z 196.0605) was present in 89.6% (n = 32) of the salicylic acid positive cases, while the [M + HCOOH + CH3 CN + Ca - H]+ adduct (m/z 264.0179) of salicylic acid was present in all positive samples with concentrations above 66 mg/kg salicylic acid. Similarly, the [M + 2Na - H]+ adduct (m/z 251.1018) of ibuprofen was present in 98.7% (n = 77) of positive cases and was present in all samples with concentrations above 3mg/kg ibuprofen.

Fatal Intoxication by the Novel Cathinone 4-Fluoro-3-methyl-α-PVP.

A 30 year old non-hispanic white male was found unresponsive at his workplace and admitted to the hospital in cardiac arrest. He was pronounced deceased shortly after arrival. At autopsy the pathologist noted a 176 pound, well-nourished, atraumatic, adult male with significant bilateral frothy pulmonary edema (right lung 930 g and left lung 1,130 g), cardiomegaly (430 g), dilated ventricles and slight cerebral edema. Upon completion of the systematic toxicological analysis scope for the Franklin County Coroner's Office Toxicology Laboratory, no known drugs were found. Further review of the gas chromatography--mass spectrometry (GC--MS) full-scan library summary reports showed an unknown peak in both the blood and urine solid phase extracts. An analogue of α-pyrrolidinovalerophenone (α-PVP) was identified, and a GC--MS selected ion monitoring method was developed to identify and quantitate the presence of 4-fluoro-3-methyl-α-PVP. This method quantified the drug at 26 ng/mL in gray top femoral blood, 30 ng/mL in purple top heart blood and 20 ng/mL in red top vitreous humor. Qualitative presence was also observed in the urine but was not detected in the liver. The decedent's cause of death was determined to be due to fluoro-methyl-PVP toxicity and the manner was ruled to be accidental. Investigational follow-up interviews corroborated drug use by the deceased with a preference of research chemicals and synthetic cannabinoids via the internet. No published literature is available currently, and to the author's knowledge this is the first incident of a fatal death solely attributed to this substituted cathinone.

Thermal (In)stability of Atropine and Scopolamine in the GC-MS Inlet.

The intoxication due to unintentional or intentional ingestion of plant material containing tropane alkaloids is quite frequent. GC-MS method is still widely used for the identification of these toxicologically important substances in human specimen. During general unknown analysis, high temperature of inlet, at least 270 °C, is commonly used for less volatile substances. Unfortunately, both tropanes are thermally unstable and could be overlooked due to their degradation. The temperature-related degradation of tropanes atropine and scopolamine was systematically studied in the inlet of a GC-MS instrument in the range 110–250 °C by increments of 20 °C, additionally also at 275 °C, and in different solvents. At inlet temperatures not higher than 250 °C, the degradation products were formed by elimination of water and cleavage of atropine’s ester bond. At higher temperatures, elimination of formaldehyde became predominant. These phenomena were less pronounced when ethyl acetate was used instead of methanol, while n-hexane proved unsuitable for several reasons. At an inlet temperature of 275 °C, tropanes were barely detectable. During systematic toxicological analysis, any tropanes’ degradation products should indicate the possible presence of atropine and/or scopolamine in the sample. It is not necessary to prepare thermally stable derivatives for confirmation. Instead, the inlet temperature can be decreased to 250 °C, which diminishes their degradation to a level where their detection and identification are possible. This was demonstrated in several case studies.

Summary statistics for drugs and alcohol concentration recovered in post-mortem femoral blood in Western Switzerland

In post-mortem investigations of fatal intoxication, it is challenging to determine which drug(s) were responsible for the death, and which drugs did not. This study aims to provide post-mortem femoral blood drug levels in lethal intoxication and in post-mortem control cases, where the cause of death was other than intoxication. The reference values could assist in the interpretation of toxicological results in the routine casework.To this end, all post-mortem toxicological results in femoral blood from 2011 to 2017 in Western Switzerland were considered. A full autopsy with systematic toxicological analysis (STA) was conducted in all cases. Results take into account the cause of death classified into one of four categories (as published by Druid and colleagues): I) certified intoxication by one substance alone, IIa) certified intoxication by more than one substance, IIb) certified other causes of death with incapacitation due to drugs, and III) certified other causes of death without incapacitation due to drugs.This study includes 1 990 post-mortem cases where femoral blood was analysed. The material comprised 619 women (31%) and 1 371 men (69%) with a median age of 50 years. The concentrations of the 32 most frequently recorded substances as well as alcohol are discussed. These include 6 opioids and opiates, 3 antidepressants, 6 neuroleptics and hypnotics, 1 barbiturate, 11 benzodiazepines (and related drugs), 2 amphetamine-type stimulants, cocaine, paracetamol, and tetrahydrocannabinol (THC).The most common substances that caused intoxication alone were morphine, methadone, ethanol, tramadol, and cocaine. The post-mortem concentration ranges for all substance are categorized as I, IIa, IIb, or III. Statistical post-mortem reference concentrations for drugs are discussed and compared with previously published concentrations. This study shows that recording and classifying cases is time-consuming, but it is rewarding in a long-term perspective to achieve a more reliable information about fatal and non-fatal blood concentrations.

Herbal Medicine Must Be Treated with Care—A Case Report on Aconitine

Pathologists usually only request a screening for natural toxic substances if plant material has been observed during autopsy or if there exists a hint in the police investigation file. This situation is aggravated by the fact that most toxins are not covered by typical immunoassays and gas chromatography–mass spectrometry (GC–MS) profiling systems. In addition, only a few forensic toxicological libraries based on liquid chromatography coupled to high-resolution tandem mass spectrometry (LC–HRMS/MS) exist. In the following case, femoral blood and urine were applied to systematic toxicological analysis (STA). However, the concentrations determined in blood did not lead to death. Consequently, a liquid chromatography high-resolution tandem mass spectrometry (LC–HRMS/MS) screening approach was applied. Aconitine was quantitated in all specimens taken during autopsy and urine and bile fluid screened for aconitine metabolites. Aconitine, jesaconitine, hypaconitine, and mesaconitine were found in the root piece collected from the duodenum. Apart from aconitine, no other alkaloids were detected in the urine or in the femoral blood sample. The highest concentrations of aconitine were found in gastric content (55.2 μg/mL), bile fluid (11.7 μg/mL), and liver (9.14 μg/g), and least in femoral blood (0.15 μg/mL) and cerebrospinal fluid (0.07 μg/mL). The liver/peripheral blood ratio amounted to 61 L/kg and indicated that aconitine undergoes postmortem redistribution. During our metabolism investigation, we found 3-dehydrogen-aconitine in the urine and bile fluid sample and N-deethyl-aconitine only in the bile fluid sample. If the routine GC–MS screening approach does not come up with a toxin, then LC–HRMS/MS profiling could represent the method of choice. In this case aconitine was identified. The concentrations determined were compared to those reported in literature and clearly indicate that the deceased died due to an aconitine overdose.

The Interest of a Systematic Toxicological Analysis Combined with Forensic Advice to Improve the Judicial Investigation and Final Judgment in Drug Facilitated Sexual Assault Cases.

The conviction rate in drug facilitated sexual assault (DFSA) cases is known to be very low. In addition, the potential impact of toxicological results on the case is often not well understood by the judicial authorities. The aims of this study were (1) to obtain more knowledge concerning the prevalence of incapacitating substances in DFSA cases, (2) to create a more efficient DFSA analysis strategy taking background information into account, and (3) to evaluate the potential impact of systematic toxicological analysis (STA) on the final judicial outcome. This small-scale epidemiological study (n = 79) demonstrates that ‘commonly-used’ illicit drugs, psychoactive medicines and ethanol are more prevalent in DFSA cases in contrast to the highly mediatized date rape drugs. Additionally, via case examples, the interest of performing STA—to prove incapacitation of the victim—in judicial procedures with mutual-consent discussions has been demonstrated as it led to increased convictions. However, more attention has to be paid to ensure a short sampling delay and to get more accurate information from the medical treatment of the alleged victim. This will improve the interpretation of the toxicological analysis and thus its applicability in a DFSA case. The future is multi-disciplinary and will certainly lead to an efficient and more cost-effective DFSA approach in which STA can impact the final judgment.

Changes in Diagnosis of Poisoning in Patients in the Emergency Room Using Systematic Toxicological Analysis with the National Forensic Service.

BackgroundIt is difficult to diagnose patients with poisoning and determine the causative agent in the emergency room. Usually, the diagnosis of such patients is based on their medical history and physical examination findings. We aimed to confirm clinical diagnoses using systematic toxicological analysis (STA) and investigate changes in the diagnosis of poisoning.MethodsThe Intoxication Analysis Service was launched in June 2017 at our hospital with the National Forensic Service to diagnose intoxication and identify toxic substances by conducting STA. Data were collected and compared between two time periods: before and after the initiation of the project, i.e., from June 2014 to May 2017 and from June 2017 to May 2020.ResultsA total of 492 and 588 patients were enrolled before and after the service, respectively. Among the 588 after-service patients, 446 underwent STA. Among the 492 before-service patients, 69.9% were diagnosed clinically, whereas the causative agent could not be identified in 35 patients. After starting the service, a diagnosis was confirmed in 84.4% of patients by performing a hospital-available toxicological analysis or STA. Among patients diagnosed with poisoning by toxins identified based on history taking, only 83.6% matched the STA results, whereas 8.4% did not report any toxin, including known substances. The substance that the emergency physician suspected after a physical examination was accurate in 49.3% of cases, and 12% of cases were not actually poisoned. In 13.4% of patients who visited the emergency room owing to poisoning of unknown cause, poisoning could be excluded after STA. Poisoning was determined to be the cause of altered mental status in 31.5% of patients for whom the cause could not be determined in the emergency room.ConclusionA diagnosis may change depending on the STA results of intoxicated patients. Therefore, appropriate STA can increase the accuracy of diagnosis and help in making treatment decisions.

Toxicological Study of an Exhumed Body Using Alternative Matrices for the Detection of Psychoactive Drugs

In forensic toxicology, systematic toxicological analyses (STA) and interpretation of results are difficult when routine matrices such as blood (typically from a central and peripheral source), urine, bile, vitreous humor, stomach or gastric contents are not available. Furthermore, in instances of limited remains, only muscle, hair, or a skeleton may be available for toxicological examination to unambiguously identify as many toxicologically relevant compounds as possible to assist in determining the cause of death. This article describes a case of the exhumed corpse of a 53-year-old male known to have been addicted to several types of drugs. The STA was carried out on alternative biological matrices, including brain, kidney and bone marrow, using gas chromatography–mass spectrometry (GC-MS) and high-performance liquid chromatography– mass spectrometry (HPLC-MS) and subsequently the identified substances were quantified by GC-MS and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The mixture found included multiple agents such as barbiturates, benzodiazepines (BZD) and anaesthetic agent. We demonstrate the possibility of detection of several drugs in an exhumed body 2 years after interment. Despite the problematic of interpreting the quantitative toxicological results, the data could provide complementary information about aetiology of death.