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1.
Chem Res Toxicol ; 37(4): 571-579, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38575522

ABSTRACT

Forensic and clinical laboratories are expected to provide a rapid screening of samples for a wide range of analytes; however, the ever-changing landscape of illicit substances makes analysis complicated. There is a great need for untargeted methods that can aid these laboratories in broad-scope drug screening. Liquid chromatography hyphenated with high-resolution mass spectrometry (LC-HRMS) has become a popular technique for untargeted screening and presumptive identification of drugs of abuse due to its superior sensitivity and detection capabilities in complex matrices. An untargeted extraction and data acquisition method was evaluated for the broad screening of high-priority drugs of abuse in whole blood. A total of 35 forensically relevant target analytes were identified and extracted at biologically relevant low and high (10× low) concentrations from whole blood using supported liquid extraction. Data-independent acquisition was accomplished using ultraperformance liquid chromatography and a quadrupole time-of-flight mass spectrometry. Results were acceptable for screening assays, with limits of detection at or below the recommended low-concentration cutoffs for most analytes. Analyte ionization varied from 30.1 to 267.6% (average: 110.5%) at low concentrations and from 8.6 to 383.5% (average: 93.6%) at high concentrations. Extraction recovery ranged from 8.5 to 330.5% (average: 105.3%) at low concentrations and from 9.4 to 127.5% (average: 82.7%) at high concentrations. This variability was also captured as precision, ranging from 4.7 to 135.2% (average: 36.5%) at low concentrations and from 0.9 to 59.0% (average: 21.7%) at high concentrations. The method described in this work is efficient and effective for qualitative forensic toxicology screening, as demonstrated by analysis of 166 authentic suspected impaired driver and postmortem specimens. That said, it is critical that laboratories establishing untargeted LC-HRMS screening assays be aware of the strengths and limitations across diverse drug categories and chemical structures.


Subject(s)
Liquid Chromatography-Mass Spectrometry , Mass Spectrometry/methods , Chromatography, Liquid/methods , Forensic Toxicology/methods , Drug Evaluation, Preclinical
2.
Anal Bioanal Chem ; 416(13): 3239-3250, 2024 May.
Article in English | MEDLINE | ID: mdl-38573343

ABSTRACT

Cocaine and antidepressants rank high globally in substance consumption, emphasizing their impact on public health. The determination of these compounds and related substances in biological samples is crucial for forensic toxicology. This study focused on developing an innovative analytical method for the determination of cocaine, antidepressants, and their related metabolites in postmortem blood samples, using unmodified commercial Fe3O4 nanoparticles as a sorbent for dispersive magnetic solid-phase extraction (m-d-SPE), coupled with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. An aliquot of 100 µL of whole blood and 5 µL of the internal standard pool were added to 30 mg of nanoparticles. The nanoparticles were separated from the sample using a neodymium magnet inserted into a 3D-printed microtube rack. The liquid was then discarded, followed by desorption with 300 µL of 1/1/1 acetonitrile/methanol/ethyl acetate. The sample was vortexed and separated, and 1.5 µL of the organic supernatant was injected into the LC-MS/MS. The method was acceptably validated and successfully applied to 263 postmortem blood samples. All samples evaluated in this study were positive for at least one substance. The most frequent analyte was benzoylecgonine, followed by cocaine and cocaethylene. The most common antidepressants encountered in the analyzed samples were citalopram and fluoxetine, followed by fluoxetine's metabolite norfluoxetine. This study describes the first report of this sorbent in postmortem blood analysis, demonstrating satisfactory results for linearity, precision, accuracy, and selectivity for all compounds. The method's applicability was confirmed, establishing it as an efficient and sustainable alternative to traditional techniques for forensic casework.


Subject(s)
Antidepressive Agents , Cocaine , Forensic Toxicology , Magnetite Nanoparticles , Solid Phase Extraction , Tandem Mass Spectrometry , Humans , Cocaine/blood , Cocaine/analogs & derivatives , Antidepressive Agents/blood , Tandem Mass Spectrometry/methods , Forensic Toxicology/methods , Solid Phase Extraction/methods , Magnetite Nanoparticles/chemistry , Chromatography, Liquid/methods , Limit of Detection , Substance Abuse Detection/methods , Male , Female , Adult
3.
J Forensic Leg Med ; 103: 102675, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38522117

ABSTRACT

This study conducts a comprehensive analysis of forensic toxicology research trends, publication patterns, author's contributions, and collaboration. Utilizing the Scopus database, we scrutinized 3259 articles across 348 journals spanning from 1975 to 2023. Analysis employed diverse software tools such as VOSviewer, RStudio, MS Excel, and MS Access to dissect various publication aspects. We observed a notable surge in publications post-2007, indicating heightened research interest. Leading contributors included the United States, Germany, and Italy, with Logan B.K. emerging as the most prolific author. Forensic Science International stood out as the primary journal, publishing 888 articles and accruing significant citations. Keyword co-occurrences such as "forensic toxicology," "forensic science," and "toxicology" underscored core thematic areas in the field. Moreover, extensive research collaboration, especially among Western nations in Europe, was evident. This study underscores the imperative for enhanced collaboration between developing and developed nations to foster further advancements in forensic science. Strengthened partnerships can catalyze innovation, facilitate knowledge dissemination, and address emerging challenges, thereby propelling the field of forensic toxicology toward new frontiers of discovery and application.


Subject(s)
Forensic Toxicology , Forensic Toxicology/trends , Humans , Bibliometrics , Periodicals as Topic/trends , Periodicals as Topic/statistics & numerical data , Biomedical Research/trends , Publishing/trends , Publishing/statistics & numerical data
4.
Article in English | MEDLINE | ID: mdl-38489939

ABSTRACT

The purpose of this study was to develop and validate a method to quantitate the veterinary sedative xylazine as well as 4-anilino-N-phenethylpiperidine (4-ANPP), acetyl fentanyl, fentanyl, norfentanyl, and p-fluorofentanyl in blood utilizing liquid chromatography tandem mass spectrometry. This method also qualitatively monitors for the presence of o-fluorofentanyl and m-fluorofentanyl isomers. UCT Clean Screen® DAU extraction columns were utilized to isolate the analytes in postmortem blood samples. The extracts were eluted, evaporated, reconstituted, and then analyzed using a Waters Acquity™ UPLC coupled a triple quadrupole mass spectrometer. The lower limit of quantitation was determined to be 0.1 ng/mL for all analytes, except for xylazine (0.2 ng/mL). The upper limit of quantitation for all analytes was 100 ng/mL. No interferences from matrix, internal standard, or common drug analytes were observed. Bias (-13.1-4.6 %) and precision (-13.14-10.3 %) fell within the acceptable ± 20 % criteria range. Dilution integrity at x2, x10, and x100 was evaluated and all results were within ± 20 % of the target concentration. Processed extract stability was evaluated after 72 h and all results were within ± 20 % of the analyte initial concentration. Matrix effects were the most prominent with xylazine, but deemed acceptable as the deuterated internal standard also observed comparable enhancement. Analysis of 89 postmortem blood samples by this method resulted in positive results for fentanyl (0.27-66 ng/mL, n = 82), xylazine (0.24-958 ng/mL, n = 21), 4-ANPP (0.10-38 ng/mL, n = 72), acetyl fentanyl (0.18-1.5 ng/mL, n = 3), p-fluorofentanyl (0.11-33 ng/mL, n = 30), and norfentanyl (0.10-98 ng/mL, n = 73).


Subject(s)
Liquid Chromatography-Mass Spectrometry , Piperidines , Xylazine , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Forensic Toxicology/methods , Fentanyl , Analgesics, Opioid
5.
Se Pu ; 42(3): 245-255, 2024 Mar 08.
Article in Chinese | MEDLINE | ID: mdl-38503701

ABSTRACT

Dried blood spot (DBS) technology is a simple and convenient method for collecting, transporting, and storing blood samples on filter paper, and has numerous applications in the clinical, research, and public health settings. This technique is gaining popularity in the field of forensic science because it facilitates the rapid analysis of prohibited drugs in blood samples and offers significant advantages in toxicology scenarios such as drinking-driving screening, drug abuse detection, and doping detection. However, the lack of a standardized system and the fact that its stability and reliability have not been thoroughly researched and demonstrated limit its application in judicial practice in China. DBS samples can be prepared, stored, and analyzed in various ways, all of which may significantly affect the results. In this study, we developed a method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) that focuses on the preparation, pretreatment, analysis, and storage of DBS samples. A thorough investigation was conducted to examine the optimal preparation conditions, including the blood spot matrix, drying technique, and preprocessing parameters, such as the solvent and extraction method. Moreover, the analytical conditions, such as the mobile phase system and elution gradient, were established to facilitate the quantitative detection of methamphetamine, lidocaine, ketamine, fentanyl, and diazepam in both DBS and whole-blood samples. The impact of storage conditions, such as the temperature, humidity, and sealing, on the analytical results of the DBS and whole-blood samples was also examined. The results showed a strong linear relationship for lidocaine and fentanyl within the range of 0.5-100 ng/mL. Similarly, methamphetamine, ketamine, and diazepam exhibited good linearity within the range of 2-100 ng/mL. The coefficients of determination (r2) ranged from 0.9983 to 0.9997, and the limits of detection ranged from 0.2 to 0.5 ng/mL, indicating a high degree of correlation and sensitivity. Stability tests demonstrated that the five target substances remained stable in the DBS for 60 days, with the measured contents deviating from the nominal values by 15%. Moreover, the measurement results of the DBS samples were highly similar to those of the whole-blood samples, with mean percentage differences of 4.44%, 3.50%, 7.66%, 5.10%, and 5.25% for fentanyl, diazepam, ketamine, lidocaine, and methamphetamine, respectively. Throughout the 60-day storage period, the maintenance of temperatures of -20 and 4 ℃, as well as sealing and dry storage, was not necessary. Room temperature was the most practical storage environment for the DBS samples. The results for each target showed very small concentration differences between the whole-blood and DBS samples, indicating that the DBS samples were suitable for drug and poison analysis in blood. Furthermore, the DBSs exhibited high quantitative consistency with the whole-blood samples, rendering them suitable matrices for preserving blood samples. Because DBS samples are easy to handle and store, they can realize the lightweight preservation of blood samples and provide a novel solution for the analysis and preservation of blood samples in public security practice. We recommend conducting comprehensive validations before utilizing DBS for analysis, particularly in terms of quantification, to ensure the judicial reliability of the results.


Subject(s)
Ketamine , Methamphetamine , Poisons , Tandem Mass Spectrometry/methods , Forensic Toxicology , Reproducibility of Results , Dried Blood Spot Testing/methods , Fentanyl , Diazepam , Lidocaine
6.
J Forensic Sci ; 69(3): 1025-1034, 2024 May.
Article in English | MEDLINE | ID: mdl-38520078

ABSTRACT

The area of forensic chemistry has been growing and developing as a line of research due to the high demands of public safety that require increasingly reliable results due to their importance in criminalistics. In this way, the development of new technologies that help this area, whether in the identification and quantification of drugs or the fight against fraud, becomes promising. In this context, the present work explored the production of reference standards from the purification of cocaine/crack samples seized by the Civil Police of the State of Espírito Santo. Cocaine was purified using chromatographic techniques, and benzoylecgonine was synthesized from purified cocaine. All substances were characterized by ultra-high-resolution mass spectrometry and nuclear magnetic resonance. Homogeneity and stability studies were also performed with benzoylecgonine, and the results were evaluated using analysis of variance (ANOVA). Cocaine and benzoylecgonine showed purities of 98.37% and 96.34%, respectively. The homogeneity of the batch, short-term stability, and other parameters were also evaluated, which together indicate this proposal as promising in the development of reference standards for drugs of abuse from samples seized by the Brazilian forensic police.


Subject(s)
Cocaine/analogs & derivatives , Illicit Drugs , Mass Spectrometry , Reference Standards , Humans , Illicit Drugs/chemistry , Magnetic Resonance Spectroscopy , Forensic Toxicology , Brazil , Gas Chromatography-Mass Spectrometry
7.
J Forensic Sci ; 69(3): 1106-1113, 2024 May.
Article in English | MEDLINE | ID: mdl-38481368

ABSTRACT

Evidence of an insulin overdose is very complicated in the medico-legal field. The analysis and subsequent interpretation of results is complex, especially when treating postmortem blood samples. The instability of insulin, the special pre-analytical conditions and the absence of specific analytical methods has led most laboratories not to analyze insulin in their routine with a consequent underestimation of cases. This paper aims to assess the difficulties associated with the analytical characterization of insulin by describing a case that typically represents most of the inconveniences encountered following a suspected insulin overdose. The case concerns a man found dead at home by his brother. After an external examination, which did not reveal a specific cause of death, toxicological analysis was requested which did not reveal any substance of toxicological interest. Only 9 months later, it was reported to the toxicologist that the subject was diabetic, on insulin lispro treatment and that three empty syringes were found next to his body. Following analysis by LC-high-resolution mass spectrometry, the presence of insulin lispro at a concentration of 1.1 ng/mL, a therapeutic concentration, was evidenced. Despite the low concentration found, overdose cannot be excluded and this paper will describe the criteria evaluated to reach this conclusion. This case highlights that the interpretation of a postmortem insulin concentration is very complex and requires the evaluation of various elements including the circumstances of death, the subject's medical history, the interval between death and sampling and the sample storage.


Subject(s)
Drug Overdose , Forensic Toxicology , Hypoglycemic Agents , Insulin Lispro , Mass Spectrometry , Humans , Male , Hypoglycemic Agents/poisoning , Chromatography, Liquid , Forensic Toxicology/methods , Insulin Lispro/poisoning , Insulin , Diabetes Mellitus , Middle Aged
8.
Toxicon ; 242: 107684, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38513827

ABSTRACT

Abrus precatorius is an herbaceous, flowering plant that is widely distributed in tropical and subtropical regions. Its toxic component, known as abrin, is classified as one of the potentially significant biological warfare agents and bioterrorism tools due to its high toxicity. Abrin poisoning can be utilized to cause accidents, suicides, and homicides, which necessitates attention from clinicians and forensic scientists. Although a few studies have recently identified the toxicological and pharmacological mechanisms of abrin, the exact mechanism remains unclear. Furthermore, the clinical symptoms and pathological changes induced by abrin poisoning have not been fully characterized, and there is a lack of standardized methods for identifying biological samples of the toxin. Therefore, there is an urgent need for further toxicopathologic studies and the development of detection methods for abrin in the field of forensic medicine. This review provides an overview of the clinical symptoms, pathological changes, metabolic changes, toxicologic mechanisms, and detection methods of abrin poisoning from the perspective of forensic toxicology. Additionally, the evidence on abrin in the field of forensic toxicology and forensic pathology is discussed. Overall, this review serves as a reference for understanding the toxicological mechanism of abrin, highlighting the clinical applications of the toxin, and aiding in the diagnosis and forensic identification of toxin poisoning.


Subject(s)
Abrin , Forensic Toxicology , Abrin/toxicity , Humans , Forensic Toxicology/methods , Abrus/chemistry
9.
J Forensic Sci ; 69(3): 1011-1020, 2024 May.
Article in English | MEDLINE | ID: mdl-38351585

ABSTRACT

Recreational methamphetamine production and heavy use can result in dwelling contamination that is difficult to detect. First responders and public health officials may use commercially available trace methamphetamine detection (presumptive) test kits to understand apparent and hidden dangers in impacted dwellings. Here, we assessed the limit of detection (LOD) of several commercially available presumptive test kits using simulated contaminated hard surfaces. Pyrex petri dishes were spiked with aliquots of methanolic methamphetamine solutions to reach desired simulated contamination levels. Commercially available presumptive tests were conducted according to manufacturer instructions and using included sample preparation materials, when available. Additionally, a laboratory-based liquid chromatography-triple quadrupole mass spectrometer (LC-MS/MS) trace methamphetamine quantification method was developed and validated using the EZSTATSG2 tool. For the LC-MS/MS method, samples were collected using 2-ply alcohol prep pads and methamphetamine was extracted using a 1:1 (v:v) methanol: water solution. Most presumptive tests considered were able to detect trace levels of methamphetamine extracted from hard surfaces, with LOD ranging from 0.10-15.00 µg/sample. Comparatively, the laboratory-based LC-MS/MS LOD was 0.05 µg/sample and limit of quantitation was 0.10 µg/sample. The LC-MS/MS method may be useful when the presence of dust or other contaminants interferes with presumptive test interpretation or reliability. Costs of presumptive tests varied from several dollars to tens of dollars, which is included alongside LOD results to aid stakeholders in identifying which test(s) are the best fit for purpose. Therefore, first responders, public health officials, and other stakeholders have several options for assessing trace methamphetamine contamination.


Subject(s)
Forensic Toxicology , Limit of Detection , Methamphetamine , Methamphetamine/analysis , Chromatography, Liquid , Humans , Forensic Toxicology/methods , Central Nervous System Stimulants/analysis , Tandem Mass Spectrometry , Surface Properties , Mass Spectrometry/methods , Liquid Chromatography-Mass Spectrometry
10.
Toxicol Sci ; 199(1): 40-48, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38366941

ABSTRACT

Organophosphorus pesticides (OPPs) having a phosphate ester moiety, such as malathion (MA) and methidathion (DMTP), are widely used and have been detected in many fatal cases of accidental exposure or suicide in Japan. In forensic toxicology, the accurate determination of blood OPP concentration is mandatory to prove death by OPP poisoning. However, fatal pesticide concentration in blood at autopsy varies depending on the circumstances surrounding the dead body. In this study, we found that 16 OPPs were degraded by human serum albumin (HSA) in a temperature-dependent fashion. The mechanism underlying MA, DMTP, azinphos-methyl, etrimfos, fenthion (MPP), pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, edifenphos (EDDP), fosthiazate, and pyraclofos degradation involves the formation of adducts with tyrosine residues in HSA. The mass spectra obtained by liquid chromatography quadrupole Orbitrap mass spectrometry revealed that phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5 were formed in HSA solution incubated with OPPs. These results indicate that the 16 OPPs are postmortem changed by HSA. The detection of phosphate ester amino acid adducts such as Y-adduct1, Y-adduct2, Y-adduct3, Y-adduct4, and Y-adduct5, instead of MA, DMTP, azinphos-methyl, etrimfos, MPP, pirimiphos-methyl, (E)-dimethylvinphos, (Z)-dimethylvinphos, vamidothion, EDDP, fosthiazate, and pyraclofos per se, may be used to determine death by these OPPs poisoning.


Subject(s)
Organophosphorus Compounds , Pesticides , Serum Albumin, Human , Tyrosine , Humans , Organophosphorus Compounds/toxicity , Organophosphorus Compounds/chemistry , Tyrosine/analogs & derivatives , Pesticides/toxicity , Pesticides/chemistry , Serum Albumin, Human/chemistry , Postmortem Changes , Chromatography, Liquid , Mass Spectrometry/methods , Forensic Toxicology/methods
11.
J Forensic Sci ; 69(3): 1021-1024, 2024 May.
Article in English | MEDLINE | ID: mdl-38362738

ABSTRACT

The conventional methamphetamine (MA) detection method using the Simon reaction can be affected by false positives owing to compounds similar to aliphatic secondary amines. In this study, we examined the new Simon reaction to improve the qualitative accuracy of MA detection to discriminate substances that give false positives in a conventional Simon reaction. After the conventional Simon reaction for MA and false positives (N-isopropylbenzylamine (NIP-BA), N-methylbenzylamine (NMe-BA), L-proline (Pro), and L-hydroxyproline (HYP)), which are colored blue, di-tert-butyl dicarbonate (t-Boc) reagent was added, and color tone changes were observed. When t-Boc was added to the false positives (NIP-BA, NMe-BA, Pro, and HYP), the colors of MA, Pro, and HYP changed to purple; NIP-BA changed to blue; and NMe-BA changed to light pink after 3 min. These results suggested that MA can be differentiated from NIP-BA and NMe-BA. Furthermore, the solid-phase chromogenic method was examined, and it was confirmed that MA could be differentiated from Pro and HYP. The method developed in this study should increase the accuracy of MA appraisal at crime scenes and contribute to the reduction of misclassifications arising from false-positive substances.


Subject(s)
Forensic Toxicology , Methamphetamine , Humans , False Positive Reactions , Forensic Toxicology/methods , Central Nervous System Stimulants/analysis , Color
12.
J Forensic Sci ; 69(3): 986-992, 2024 May.
Article in English | MEDLINE | ID: mdl-38402540

ABSTRACT

The increasing use and misuse of gabapentin pose a major risk to public health and traffic safety. Gabapentin has been approved by the Food and Drug Administration (FDA) since 1993 for adjunctive therapy in the treatment of epilepsy and neuralgia but is increasingly being prescribed for numerous off-label uses including insomnia, anxiety, depression, and migraine. Reported side effects include blurred vision, drowsiness, and loss of coordination. Driving behaviors such as exiting the lane of travel and crashes have been reported in connection to drugged driving investigations concerning gabapentin. To further assist with the toxicological interpretation of gabapentin in driving under the influence of drugs (DUID) scenarios, a review of approximately 108,000 gabapentin-positive DUID cases was conducted. Of those, 858 cases met inclusion criteria and underwent additional evaluation. Blood specimens were screened via enzyme-linked immunosorbent assay (ELISA) and confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for quantitation of gabapentin. This review found an overall DUID gabapentin positivity of 7.9% between January 2020 and December 2022; 17 states from various geographical regions had at least one positive gabapentin DUID case. Observations in six driving and human performance cases where gabapentin was the only drug reported were consistent with the known adverse effects of the medication. Half of the case histories reviewed involved crashes where the driver was determined to be at fault. Additionally, 94% of the cases in this review involved gabapentin in combination with other drugs. The most prevalent drug combinations were opioids and gabapentin present in 64% of cases.


Subject(s)
Driving Under the Influence , Gabapentin , Tandem Mass Spectrometry , Humans , Chromatography, Liquid , Male , Enzyme-Linked Immunosorbent Assay , Adult , Female , Middle Aged , Forensic Toxicology
13.
J Forensic Sci ; 69(3): 974-985, 2024 May.
Article in English | MEDLINE | ID: mdl-38317608

ABSTRACT

Ethanol is the psychoactive substance identified most frequently in post-mortem specimens. Unfortunately, interpreting post-mortem ethanol concentrations can be difficult because of post-mortem alcohol redistribution and the possibility of post-mortem alcohol neogenesis. Indeed, in the time interval between death and sample collection, the decedent may be exposed to non-controlled environments for an extended period, promoting microbial colonization. Many authors report that in the presence of carbohydrates and other biomolecules, various species of bacteria, yeast, and fungi can synthesize ethanol and other volatile substances in vitro and in vivo. The aim of this study was to study the impact of several variables on microbial ethanol production as well as develop a mathematical model that could estimate the microbial-produced ethanol in correlation with the most significant consensual produced higher alcohol, 1-propanol. An experimental setup was developed using human blood samples and cadaveric fragments incubated under strictly anaerobic conditions to produce a novel substrate, "cadaveric putrefactive blood" mimicking post-mortem corpse conditions. The samples were analyzed daily for ethanol and 1-propanol using an HS-GC-FID validated method. The formation of ethanol was evaluated considering different parameters such as putrefactive stage, blood glucose concentration, storage temperature, and storage time. Statistical analysis was performed using the Mann-Whitney non-parametric test and simple linear regression. The results indicate that the early putrefactive stage, high blood glucose concentration, high temperature, and time of incubation increase microbial ethanol production. In addition, the developed mathematical equation confirms the feasibility of using 1-propanol as a marker of post-mortem ethanol production.


Subject(s)
1-Propanol , Ethanol , Postmortem Changes , Proof of Concept Study , Humans , Ethanol/analysis , Specimen Handling , Chromatography, Gas , Biomarkers/analysis , Biomarkers/metabolism , Central Nervous System Depressants/analysis , Forensic Toxicology , Blood Alcohol Content , Cadaver , Temperature , Models, Theoretical , Flame Ionization
15.
Sud Med Ekspert ; 67(1): 40-46, 2024.
Article in Russian | MEDLINE | ID: mdl-38353014

ABSTRACT

OBJECTIVE: Is to develop a method for determining 2.4-dimethylhydroxybenzene (2.4-DMHOB) in biological material. The analytical methods used in the experiments were extraction, column chromatography of normal pressure, TLC, GC-MS and HPLC. To extract the analyte from the bioactive matrix, maceration with the binary insulating agent acetone-ethyl acetate (3:7) was used, observing the 2:1 mass ratio of the «insulating agent-matrix¼. Optimal conditions of semi-preparative analyte chromatography were achieved in column (150×10 mm) of «Silasbor¼ S-18 sorbent in elution with a mixture of acetonitrile-water (7:3), which was used in the proposed cleaning scheme, combining extraction and reversed-phase column chromatography. The application of the mobile phase of tetrachloromethane-dioxane (9.5:0.5) has been substantiated for the selective determination of 2.4-DMHOB by TLC («Sorbfil¼ plates). The expediency of confirming identification of the analyte in the form of 2.4-dimethyltrymethylsilylphenol using GC-MS (DB-5MS EVIDEX column (25.000×0.2 mm), stationary phase (5%-phenyl)-methylpolysiloxane, carrier gas - helium) has been shown. The group of characteristic particles in the mass spectrum of trimethylsilyl analyte derivative was represented by 45; 59; 73; 82; 91; 105; 119; 135; 149; 163; 179; 194 m/z ions. HPLC (Discovery C18 250×4.6 mm column, eluting liquid - acetate buffer solution with pH 5.5 - acetonitrile, 50:50) was used to confirm the identification and quantification of 2.4-DMHOB. A method for determining 2.4-DMHOB by the HPLC method in biological material (liver tissue) is proposed, which corresponds to the criteria of linearity, selectivity, accuracy, precision and stability. The minimum detectable quantity of 2.4-DMHOB in the bioactive matrix is 0.5 µg/g, the minimum determined quantity is 1.2 ug/g.


Subject(s)
Acetone , Gas Chromatography-Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Forensic Toxicology , Acetonitriles
16.
Leg Med (Tokyo) ; 68: 102400, 2024 May.
Article in English | MEDLINE | ID: mdl-38237272

ABSTRACT

A man in his 50 s, who was found vomiting and in a disturbed state when the emergency medical team arrived, then went into cardiopulmonary arrest during transport and died without responding to resuscitation. The hospital initially suspected that the death may have been caused by internal causes, but since the deceased had previously been transported to the hospital in a suicide attempt, the hospital called police regarding suspicions of unnatural death. The police investigation revealed two empty bottles of nicotine liquid for e-cigarettes in his house and a search history of "nicotine suicide" on his cellphone. In a forensic autopsy, he was found to be highly obese, and abundant fat deposits were observed in his organs. A stent was placed in the aorta, but no abnormality was found. There was no obvious stenosis or obstruction in the coronary arteries. Drug screening using liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed on cardiac blood, urine, and stomach contents collected at autopsy, which revealed the presence of some medical products such as aripiprazole, nicotine, and cotinine. Further quantitative testing revealed high concentrations of nicotine in all samples. The left and right femoral venous blood concentrations were above the lethal dose, suggesting that arrhythmia or respiratory failure due to nicotine intoxication was the cause of death. With the widespread use of e-cigarettes, high concentrations of nicotine are readily available, and case reports of serious nicotine addiction are increasing. It is important to always consider addiction when conducting forensic evaluations in the medical field.


Subject(s)
Autopsy , Nicotine , Suicide, Completed , Humans , Male , Nicotine/poisoning , Nicotine/analysis , Middle Aged , Chromatography, Liquid , Tandem Mass Spectrometry , Electronic Nicotine Delivery Systems , Gastrointestinal Contents/chemistry , Forensic Toxicology
17.
Forensic Sci Med Pathol ; 20(1): 100-105, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37060536

ABSTRACT

Ramipril is a popular angiotensin-converting enzyme inhibitor applied in the treatment of hypertension. Its therapeutic effect is oriented on the concentration of the active metabolite ramiprilat. The information about toxic drug levels is missing in the literature. Therefore, the aim of this work was an indication of possible toxic ranges based on the analysis of real samples with high ramiprilat concentrations. For these purposes, an appropriate analytical LC-MS/MS method was developed and validated according to forensic guidelines and applied in the routine. Most real samples targeted for ramipril/ramiprilat were associated with the typical therapeutic drug range of 1-40 ng/mL described in the literature. However, higher drug levels with ramiprilat concentrations above 100 ng/mL could also be observed infrequently in cases of driving under the influence of drugs or attempted suicides. To the best of the author's knowledge, this is the first time antemortem ramipril and ramiprilat concentrations associated with driving under the influence of drugs and suicide attempts were discussed from a forensic point of view. The collected data enabled an indication of the ramiprilat toxic concentration range from about 600 ng/mL to at least 3500 ng/mL. The toxic concentration range discussed can be applied in the forensic practice as a reference for future cases.


Subject(s)
Ramipril/analogs & derivatives , Tandem Mass Spectrometry , Humans , Chromatography, Liquid , Forensic Toxicology
18.
Am J Forensic Med Pathol ; 45(1): 67-71, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38064344

ABSTRACT

ABSTRACT: Umbilical cord tissue (UCT) traditionally has been used as an antemortem matrix for identifying and monitoring fetal exposure to drugs suspected to have been used during pregnancy. The specimen offers several advantages as a testable tissue, including accessibility and ease of collection, ample sample volume, a long window of detection, and ability to detect for a wide range of drugs. Despite these advantages, little to no research exists on the use of UCT as a postmortem forensic toxicology specimen. This article aims to provide insights into UCT toxicological testing and infer potential applications for postmortem use, such as investigations into stillbirths and infant abandonment. Umbilical cord tissue offers several benefits as a postmortem toxicological specimen. Importantly, it can be collected with or without an autopsy being performed and may help explain factors that contribute to the underdevelopment and death of the neonate. With the limited sample volumes present in infant investigations, toxicological analysis of UCT could become a valuable tool for neonatal medicolegal death investigations.


Subject(s)
Umbilical Cord , Infant, Newborn , Pregnancy , Infant , Female , Humans , Autopsy , Forensic Toxicology
19.
Int J Legal Med ; 138(2): 415-430, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37768350

ABSTRACT

INTRODUCTION: Proactive drug facilitated crime (DFC) is the administration of psychoactive substances (PAS) for criminal purposes without the victim's knowledge or by force. In Paris, France, patients who report suspected proactive DFC to the police are examined at the Department of Forensic Medicine (DFM) of the Hôtel-Dieu Hospital. Preventively blood and urine samples are collected but not systematically analyzed by the judicial authority. We aimed to assess the proportion of probable proactive DFC in patients examined at the Hôtel-Dieu DFM following a police report for suspected proactive DFC. METHOD: Blood and urine samples were collected from 100 patients. Toxicological analyses were performed by the toxicology laboratory of the Lariboisière Hospital. The results were correlated with the clinical data collected at the initial and follow-up consultations. RESULTS: At least one PAS was detected in 86% of the cases (voluntary or involuntary intake). After correlation with clinical data, 32% of the cases were classified as probable proactive DFC. In these cases, 49% of the substances identified were illicit substances (amphetamines, MDMA, etc.); 16% were benzodiazepines and related substances; 16% were antihistamines and sedatives; 14% were opioids; and 5% were antidepressants and anti-epileptics. In 90% of the cases, patients reported a voluntary ethanol consumption in the hours prior to the suspected proactive DFC. CONCLUSION: Toxicological analyses revealed a high proportion of both probable proactive DFC and probable opportunistic DFC. Our results indicate the need to perform systematical toxicological analysis in cases of suspected DFC.


Subject(s)
Crime Victims , Prodrugs , Sex Offenses , Substance-Related Disorders , Humans , Substance-Related Disorders/epidemiology , Crime , Hypnotics and Sedatives , Forensic Medicine/methods , Forensic Toxicology
20.
J Anal Toxicol ; 48(1): 1-8, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-37889229

ABSTRACT

Soon approaching its 50th anniversary, Journal of Analytical Toxicology (JAT) is an international scholarly publication specializing in analytical and forensic aspects of toxicology. Science Citation Index (SCI) and Journal Citation Reports (JCR), both of which are part of the Web-of-Science (WOS) database, were used to make a bibliometric evaluation of JAT articles. Between 1977 (volume 1) and 2023 (volume 47), a total of n = 4,785 items were published in JAT; the top-ten most highly cited articles and the most prolific authors were identified. Changes in the journal impact factor (JIF) were studied between 1997 and 2022, and this metric varied from a low of 1.24 (2006) to a high of 3.36 (2020).The most recent JIF (2022) dropped to 2.5 and the corresponding 5 year JIF was 2.6. JAT's most highly cited article (590 cites) was a working group (SWGTOX) report dealing with standard practices for the validation of analytical methods in forensic toxicology laboratories. JAT published 62 articles each of which were cited over 100 times and the H-index for JAT was 89. The most prolific author of JAT articles was credited with 119 items, the first in 1980 (volume 4) and the latest in 2023 (volume 47). JAT articles were cited 4,537 times in 2022 by all journals in the JCR database, although 520 of these were self-citations (11.5%). Bibliometric methods are increasingly used to evaluate the published work of individual scientists, university departments, entire universities and whole countries. Highly cited articles are considered more influential and authoritative compared with papers that are seldom or never cited.


Subject(s)
Bibliometrics , Humans , Forensic Toxicology
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