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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 29871

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Special Issue Editors

Prof. Dr. Grzegorz Teresinski

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Guest Editor

Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland
Interests: forensic medicine; forensic toxicology; postmortem markers; tanatochemistry; biomechanics

Prof. Dr. Grzegorz Buszewicz

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Co-Guest Editor

Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland
Interests: forensic toxicology; HPLC-MS/MS; public health; epidemic; pharmaceutical preparation; diagnosis

Dr. Jacek Baj

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Co-Guest Editor

Department of Correct Anatomy, Medical University of Lublin, 20-090 Lublin, Poland
Interests: fatty liver disease; liver diseases; cholecystectomy; micronutrients; macronutrients
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Special Issue Information

Dear Colleagues,

Forensic toxicology is a contractual section of applied toxicology that has relevant to medical knowledge and technology for litigious purposes. This field uniquely combines the scientific foundations of a wide range of biological and physical fields as well as the achievements of its methodology to obtain professional evidence in proceedings verifying compliance with specific legal standards.

Forensic toxicology tries to verify the cases in which the causes of toxic or psychoactive substances usage have administrative or medico-legal consequences regarding both living and dead subjects. This interdisciplinary field extracted from clinical chemistry, medicine, and pharmacology involves the medical basis of analytical chemistry undertaken to confirm or exclude the presence of xenobiotics in the biological and non-biological material as well as the interpretation of the results of the analysis for legal purposes.

Fields of forensic toxicology include:

diagnosis of fatal intoxications in case of deliberate or accidental cases in criminal investigations;
detection of the substances used in criminal activities as well as doping in sport;
identifications of medicine or illicit drugs in different biological matrices (also postmortem);
the assessment of the influence of drugs and medicaments on the psychomotor performance (driving under the influence of alcohol or drugs, substance abuse in the workplace);
identification and analysis of psychoactive substances in seized materials;
development of novel analytical methods and/or improvement of laboratory investigation strategy;
analysis and interpretation of toxicologic markers for the application of justice.

Analytical methods used in forensic toxicology must be characterized by the highest quality to provide reliable results of the analyses. Any analytical procedures must be checked in terms of validation standards and referenced methods taking into account the biological matrix which includes the examined substance. Current forensic toxicology, for confirmatory analyses, uses advanced instrumental techniques of chromatographic separation of gas or liquid phase coupled with mass spectrometry. The sensitivity and selectivity of tandem mass spectrometers enable the detection of nanomolar concentrations of analytes in a variety of research materials.

The advancements in analytical techniques enabled a dynamic growth of forensic biochemistry and tanatochemistry. Tanatochemistry research is mostly focused on the biochemical indicators of metabolic disorders that usually occur in very small concentrations. Nanochemical markers reflect the pathologic processes appearing in the perimortem period helping in the identification of the cause of death along with the circumstances of death for the elucidation of events of judicial importance.

We are pleased to invite contributors to this collection of Toxics which will focus on various aspects of forensic toxicology and related topics. We invite all the papers addressing this problem. Studies that use metabolomics and deal with tanatochemistry are also encouraged. This Special Issue aims to highlight and collect research on the established knowledge, as well as on other issues, providing new starting points for future advances. Original research articles and reviews are particularly welcomed. Short communications and meta-analyses would also be accepted that focus on the problems underlying the analytical performance and the challenges of modern forensic toxicology. Studies may include, but are not limited to:

postmortem forensic toxicology;
synthetic and natural poisons;
data acquisition/interpretation, with particular emphasis on post-mortem data;
development and application of novel analytical methods;
interpretation of forensic toxicological data;
screening of medicines, drugs of abuse, and alcohol in clinical and forensic specimens;
new psychoactive substances;
human performance toxicology;
strategies for an appropriate impairment judgment;
driving under the influence of drugs and alcohol;
doping control (sports performance tests);
workplace drug tests;
latest advances in biomarker-related research;
application of proteomics to forensic toxicology;
markers of necrochemical diagnostics

Prof. Dr. Grzegorz Teresinski
Prof. Dr. Grzegorz Buszewicz
Dr. Jacek Baj
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

forensic toxicology
forensic analytical chemistry
postmortem toxicology
drugs of abuse detection
biological matrices
post-mortem specimens
separation analytical techniques
gas/liquid chromatography
tandem mass spectrometry
analytical method validation
accuracy, validity, and reliability of diagnostic methods
interpretation of analysis results
forensic alcohology
drug-impaired driving
new psychoactive substances
forensic biochemistry
tanatochemistry biomarkers

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Published Papers (10 papers)

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13 pages, 3358 KiB

Open AccessArticle

Metabolic Evaluation of Synthetic Opioids on the Example of U-47700 with the Use of In Vitro and In Vivo Methods for Forensic Toxicology Application

by Sebastian Rojek, Ewa Poljańska, Weronika Chaim, Martyna Maciów-Głąb and Beata Bystrowska

Toxics 2023, 11(3), 220; https://doi.org/10.3390/toxics11030220 - 25 Feb 2023

Cited by 2 | Viewed by 2158

Abstract

Legal highs present a great threat to health, especially in groups of people experimenting with psychoactive substances. The lack of available knowledge on the biotransformation of these substances necessitates symptomatic treatment in the event of intoxication, which, unfortunately, may be ineffective. Opioids, including heroin analogues, such as U-47700, constitute a special group of designer drugs. In this study, a multi-directional approach to trace the biotransformation of U-47700 in living organisms was used. For this purpose, the in silico assessment (ADMET Predictor) was used first and then followed by an in vitro study using human liver microsomes and the S9 fraction. The biotransformation was then followed in an animal model (Wistar rats). Tissues such as blood, brain and liver were collected for analysis. The study was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The obtained results were compared to those obtained from the analysis of autopsy materials (cases analysed in the Toxicology Laboratory of the Department of Forensic Medicine, Jagiellonian University Medical College in Krakow). Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

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8 pages, 2088 KiB

Open AccessCommunication

Epiglottis Cartilage, Costal Cartilage, and Intervertebral Disc Cartilage as Alternative Materials in the Postmortem Diagnosis of Methanol Poisoning

by Marcin Tomsia, Elżbieta Chełmecka, Małgorzata Głaz and Joanna Nowicka

Toxics 2023, 11(2), 152; https://doi.org/10.3390/toxics11020152 - 5 Feb 2023

Cited by 1 | Viewed by 1722

Abstract

Alternative materials for postmortem diagnosis in the case of fatal poisonings are much needed when standard materials, such as blood and urine, are unavailable. The study presents a case of fatal mass methanol intoxication resulting from industrial alcohol consumption. The study aimed to determine methanol and formic acid concentrations in epiglottis cartilage, costal cartilage, and intervertebral disc cartilage and to analyze the correlation between their concentrations in cartilage tissues and the femoral blood. Methanol and formic acid concentrations in samples collected from 17 individuals (n = 17) were estimated using gas chromatography with flame ionization detection (GC-FID). Methanol concentration in the costal cartilage correlated with its concentration in the femoral blood (r = 0.871). Similar correlations were found for epiglottis cartilage (r = 0.822) and intervertebral disc cartilage (r = 0.892). Formic acid concentration in the blood correlated only with its concentration in urine (r = 0.784) and the epiglottis (r = 0.538). Cartilage tissue could serve as an alternative material for methanol analyses in postmortem studies. Formic acid, a methanol metabolite, does not meet the requirements for its presence determination in cartilage tissues. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

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7 pages, 262 KiB

Open AccessArticle

Fatal Methanol Poisoning Caused by Drinking Industrial Alcohol: Silesia Region, Poland, April–June 2022

by Marcin Tomsia, Małgorzata Głaz, Joanna Nowicka, Julia Cieśla, Maciej Sosnowski and Elżbieta Chełmecka

Toxics 2022, 10(12), 800; https://doi.org/10.3390/toxics10120800 - 19 Dec 2022

Cited by 5 | Viewed by 3024

Abstract

Methanol poisonings caused by drinking industrial alcohol remain a severe problem worldwide. Education on types of alcohol and their harmfulness and legal regulations limiting the industrial alcohol trade seem to be the keys to reducing the number of poisonings. Methanol distribution in different tissues after absorption is not well understood. This research aimed to quantify the methanol and formic acid distribution in body fluids and tissue material in post-mortem samples collected from 19 fatal victims of massive intoxication with industrial alcohol in the Silesia Region (Poland) who died between April and June 2022. The samples were analyzed using a gas chromatography–flame ionization detector (GC-FID), and correlation coefficients for methanol and formic acid were determined. The results show a wide distribution of methanol and formic acid in human post-mortem biological fluids (blood, urine, vitreous humor, bile, and cerebrospinal fluid) and tissues (muscle, kidney, liver, spleen, lung, and brain). The strongest correlation for methanol concentration in blood and body fluids/tissues was obtained in the cerebrospinal fluid (r = 0.997) and for formic acid in muscle tissue (r = 0.931). The obtained results may be a valuable tool in toxicological analysis and improve medical standards of early diagnosis and targeted treatment. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

8 pages, 274 KiB

Open AccessArticle

A Case of Amphetamine and Methamphetamine Intoxication in Cat

by Agnieszka Chłopaś-Konowałek, Kaja Tusiewicz, Olga Wachełko, Paweł Szpot and Marcin Zawadzki

Toxics 2022, 10(12), 749; https://doi.org/10.3390/toxics10120749 - 1 Dec 2022

Cited by 3 | Viewed by 2995

Abstract

Stimulants belonging to the amphetamine group nowadays pose an undeniable worldwide threat to the life and health of users. Intoxications of domestic animals also occur, which can either be accidental or related to intentional human action. This study presents the first ever reported case of a simultaneous amphetamine and methamphetamine intoxication of a cat, along with the results of toxicological studies. Blood, urine, vitreous humor and liver were collected during the cat’s autopsy and analyzed by UHPLC─QqQ─MS/MS. The sample preparation technique was based on one-step precipitation of proteins with cold acetonitrile. The determined amphetamine concentrations in the collected biological materials were 93.4 ng/mL in blood, 496.6 ng/mL in urine, 589.2 ng/mL in the vitreous humor and 291.2 ng/g in liver, respectively. Methamphetamine concentrations were 45.5 ng/mL in blood, 263.1 ng/mL in urine, 351.2 ng/mL in vitreous humor, and 97.7 ng/g in liver. Other substances were also found in the biological material, i.e., diazepam, oxazepam and nordiazepam. Cases of intentional or accidental poisoning of pets with psychoactive substances are a serious problem, carrying the risk to the health and life of the animal. Therefore, it is important to increase awareness of the high risk of poisoning of domestic animals, as well as to learn about the incompletely understood mechanisms of pharmacokinetics of various drugs in animals, including cats. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

9 pages, 1249 KiB

Open AccessFeature PaperArticle

Diffusion of Carbon Monoxide and Hydrogen Cyanide to Muscles and Blood—An Experimental Study

by Jacek Baj, Grzegorz Buszewicz, Dominika Przygodzka, Alicja Forma, Jolanta Flieger and Grzegorz Teresiński

Toxics 2022, 10(11), 707; https://doi.org/10.3390/toxics10110707 - 18 Nov 2022

Cited by 2 | Viewed by 2102

Abstract

Postmortem carbon monoxide (CO) and hydrogen cyanide (HCN) diffusion under ambient conditions was assessed in a human cadaver model. The main objective of this study was to determine whether the postmortem diffusion of HCN and CO greatly affected the determination of HCN, carboxyhemoglobin (COHb), and carboxymyoglobin (COMb). Layered samples of blood, musculocutaneous, and muscular specimens were collected from the adult cadavers and placed in the tight chambers designed for the purpose of this experiment. The specimens were treated with CO and HCN for 24 h. COHb and COMb were determined using headspace gas chromatography (GC) with an O-FID detector while the HCN values were assessed using a GC headspace with an NPD detector. It was shown that the skin substantially limited the diffusion of CO which penetrated the superficial layers of the muscle very slightly, all the while not affecting the blood level of COHb in the 4.5 cm layer of the muscle located underneath. There were no differences regarding the CO diffusion between superficially charred and thermally coagulated compared to that observed in intact integuments. In addition, the cutaneous sample deprived of the adipose layer was not shown to be a barrier to the moderate diffusion of CO into the blood layer below. HCN was found to easily diffuse from the skin to the blood vessels (vein specimens), and partial charring and thermocoagulation of the superficial muscular layer favored the diffusion of cyanides into the tissues. Similarly to CO, HCN diffusion to the blood and muscles was greatly limited by the adipose layer. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

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12 pages, 958 KiB

Open AccessArticle

Toxicological Aspects of Methotrexate Intoxication: Concentrations in Postmortem Biological Samples and Autopsy Findings

by Paweł Szpot, Olga Wachełko and Marcin Zawadzki

Toxics 2022, 10(10), 572; https://doi.org/10.3390/toxics10100572 - 29 Sep 2022

Cited by 2 | Viewed by 4049

Abstract

The aim of this study was the establishment of a UHPLC-QqQ-MS/MS method to determine methotrexate in postmortem biological samples and quantify the postmortem distribution of methotrexate in a case of fatal intoxication of this drug. A volume of 100 μL or 100 mg of postmortem specimens was precipitated with 400 μL of cold methanol and then analyzed using UHPLC-QqQ-MS/MS. The validation parameters of the method were as follows: limit of quantification: 0.1–1.0 ng/mL or ng/g, coefficient of determination: >0.998 (R²), matrix effect, intra- and inter-day accuracies and precisions: not greater than 13.6%, 14.8% and 17.4%, respectively. The recoveries were: 89.0–113.6%. The postmortem distribution studies revealed methotrexate concentrations as follows: blood—7.2 ng/mL, vitreous humor—0.8 ng/mL, liver—43.7 ng/g, kidney—20.6 ng/g, bone marrow—29.9 ng/g, lumbar vertebra—20.0 ng/g. The highest concentrations of methotrexate after poisoning were found in the tissues with the most rapidly dividing cells. The method described is simple, precise and selective. Methotrexate concentrations can be routinely determined in postmortem specimens. Determination of methotrexate in the postmortem biological material is possible after a few days of intensive treatment. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

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15 pages, 3144 KiB

Open AccessArticle

Diclofenac Concentrations in Post-Mortem Specimens—Distribution, Case Reports, and Validated Method (UHPLC-QqQ-MS/MS) for Its Determination

by Paweł Szpot, Olga Wachełko and Marcin Zawadzki

Toxics 2022, 10(8), 421; https://doi.org/10.3390/toxics10080421 - 26 Jul 2022

Cited by 9 | Viewed by 3482

Abstract

The aim of the research was to establish a sensitive method for the quantification of diclofenac in postmortem samples. The developed method was applied in six cases: three fetuses in which the use of abortion pills by their mothers was suspected, one case of duodenal ulcer perforation, one case of traffic accident with fatal outcome, and one acute renal failure in which the distribution of diclofenac was examined. The analyses were performed using liquid–liquid extraction of postmortem samples and the quantification of diclofenac via ultra-high performance liquid chromatography, coupled with triple quadrupole tandem mass spectrometry. Gradient elution using a C18 column was applied. Electrospray ionization measurement in positive multiple reaction monitoring mode was used. Diclofenac-d4 was used as an internal standard. The validation parameters were as follows: lower limit of quantification: 0.5 ng/mL, linearity of calibration curve: 0.5–500 ng/mL, intra- and interday accuracies and precisions: not greater than 15%; recovery values: 72.0–102.2%, and matrix effect: 2.2–28.0%. The developed method enabled the determination of diclofenac in human postmortem biological fluids (blood, urine, vitreous humor, bile, and stomach content), tissues (placenta, kidney, liver, and heart), and in exhumated fetus bones, with high recovery, sensitivity, precision, and accuracy. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

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Review

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23 pages, 1927 KiB

Open AccessReview

Selected Political Criminal Poisonings in the Years 1978–2020: Detection and Treatment

by Zuzanna Brunka, Jan Ryl, Piotr Brushtulli, Daria Gromala, Grzegorz Walczak, Sonia Zięba, Dorota Pieśniak, Jacek Sein Anand and Marek Wiergowski

Toxics 2022, 10(8), 468; https://doi.org/10.3390/toxics10080468 - 12 Aug 2022

Cited by 8 | Viewed by 3625

Abstract

Criminal poisonings are among the least frequently detected crimes in the world. Lack of suspicion of this type of event by police officers and prosecutors, clinical symptoms imitating many somatic diseases and technical difficulties in diagnostics, as well as high research costs make the actual frequency of these events difficult to estimate. The substance used for criminal poisoning is often characterized by: lack of taste, color and smell, delayed action, easy availability and difficulty to detect. The aim of the study was to analyze selected cases of political poisoning that took place in the years 1978–2020, to describe the mechanisms of action of the substances used and to evaluate the diagnosis and treatment. The analyzed cases of criminal poisoning concerned: Georgi Markov (ricin), Khalid Maszal (fentanyl), Wiktor Yushchenko (TCDD dioxin), Jasir Arafat (polonium ²¹⁰Po isotope), Alexander Litvinenko (polonium ²¹⁰Po isotope), Kim Jong-Nam (VX), Sergei Skripal (Novichok) and Alexei Navalny (Novichok). Contemporary poisons, to a greater extent than in the past, are based on the use of synthetic substances from the group of organophosphorus compounds and radioactive substances. The possibility of taking appropriate and effective treatment in such cases is the result of many factors, including the possibility of quick and competent rescue intervention, quick and reliable detection of the toxic substance and the possibility of using an antidote. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

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15 pages, 681 KiB

Open AccessReview

Current Progress for Retrospective Identification of Nerve Agent Biomarkers in Biological Samples after Exposure

by Jin Wang, Xiaogang Lu, Runli Gao, Chengxin Pei and Hongmei Wang

Toxics 2022, 10(8), 439; https://doi.org/10.3390/toxics10080439 - 1 Aug 2022

Cited by 3 | Viewed by 2377

Abstract

Organophosphorus neurotoxic agents (OPNAs) seriously damage the nervous system, inhibiting AChE activity and threatening human health and life. Timely and accurate detection of biomarkers in biomedical samples is an important means for identifying OPNA exposure, helping to recognize and clarify its characteristics and providing unambiguous forensic evidence for retrospective research. It is therefore necessary to summarize the varieties of biomarkers, recognize their various characteristics, and understand the principal research methods for these biomarkers in the retrospective detection of OPNA exposure. Common biomarkers include mainly intact agents, degradation products and protein adducts. Direct agent identification in basic experimental research was successfully applied to the detection of free OPNAs, however, this method is not applicable to actual biomedical samples because the high reactivity of OPNAs promotes rapid metabolism. Stepwise degradation products are important targets for retrospective research and are usually analyzed using a GC–MS, or an LC–MS system after derivatization. The smaller window of detection time requires that sampling be accomplished within 48 h, increasing the obstacles to determining OPNA exposure. For this reason, the focus of retrospective identification of OPNA exposure has shifted to protein adducts with a longer lifetime. Compared to the fluoride-induced reactivation method, which cannot be used for aged adducts, digestive peptide analysis is the more elegant method for detecting various adducts, identifying more active sites, exploring potential biomarkers and excavating characteristic ions. Retrospective identification of biomarkers after OPNA poisoning is of primary importance, providing unambiguous evidence for forensic analysis in actual cases and judgment of chemical accidents. At present, degradation products, the nonapeptide from BChE adducts and Y411 from human serum adducts are used successfully in actual cases of OPNA exposure. However, more potential biomarkers are still in the discovery stage, which may prove inconclusive. Therefore, there is an urgent need for research that screens biomarker candidates with high reactivity and good reliability from the potential candidates. In addition, mass spectrometry detection with high resolution and reactivity and an accurate data processing system in the scanning mode must also be further improved for the retrospective identification of unknown agents. Full article

(This article belongs to the Special Issue Advance in Forensic Toxicology)

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9 pages, 246 KiB

Open AccessCase Report

Fatal Suicidal Intoxication with Pentoxifylline Complicated by Cardiovascular Disorders

by Jacek Sein Anand, Marek Wiergowski, Marek Roman Wiśniewski, Monika Kosmowska, Marzena Kata and Mateusz Kacper Woźniak

Toxics 2022, 10(8), 447; https://doi.org/10.3390/toxics10080447 - 3 Aug 2022

Cited by 1 | Viewed by 2468

Abstract

Pentoxifylline is a xanthine derivative used in vascular disorders that is recognized as a safe drug for patients. The paper describes a rare case of fatal and suicidal pentoxifylline poisoning in an 82-year-old man with multiple preexisting diseases (arterial hypertension, coronary artery disease, type 2 diabetes, and intermittent claudication). The patient was admitted to the clinical toxicology unit approximately 2 h after the overdose and died 36 h after the admission despite intensive care. Multiple arterial blood gas analyses and other laboratory tests were performed during the hospitalization and are reported in the paper. Postmortem examination of the biological material was carried out with the use of histopathological techniques. The toxicological studies using chromatographic techniques coupled with mass spectrometry showed that postmortem blood levels of pentoxifylline have been found in the range which is described in the available literature to be toxic and lethal. The analysis of test results and clinical data showed that the patient died as a result of increasing circulatory and respiratory failure, complicated by disorders of the acid-base and electrolyte balance (respiratory alkalosis, concomitant lactic acidosis, and hypokalemia), hyperglycemia, and coagulation disorders. Full article

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