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Aims Methods Results Conclusion Since their emergence on the drug market, synthetic cannabinoids (SC) are still gaining increasing importance in forensic toxicology. The representatives of the so‐called new psychoactive substances have in common that they have not undergone preclinical safety studies. Hence, knowledge on toxicokinetic (TK) data is sparse. As an alternative to human studies not being allowed for ethical reasons, a sophisticated pig model was applied in the present study to assess the TK of the SC 5F‐MDMB‐P7AICA.Pigs pulmonarily received 5F‐MDMB‐P7AICA via an ultrasonic nebulizer. The parent compound and its main metabolite 5F‐MDMB‐P7AICA dimethyl butanoic acid were determined in serum and whole blood using liquid chromatography–tandem mass spectrometry. Obtained data was analysed by population (pop) TK modelling. The final pop TK model parameters for pigs were upscaled via allometric scaling techniques for the prediction of human exposure.The serum concentration–time profiles of the parent and the pop TK analysis revealed that a 4‐compartment model best describes the TK data. The administration of the aerosol into the lung compartment follows zero‐order kinetics. A transit compartment was further included to accurately describe the time delay between detection of the parent and the metabolite. Despite the different structure, TK parameters were found to be comparable to other examined SC.The predictions of human SC exposure suggest that multiple administration of 5F‐MDMB‐P7AICA substantially enhances the window of detection. The simulations pose extrapolation of the data used for model development with respect to dose linearity and allometric scaling to humans. [ABSTRACT FROM AUTHOR]

A 77‐year‐old professional gold craftsman ingested a white powder used in goldsmithing, mistaking the powder for a health supplement. He detected a strange taste and immediately fell sick, reported the incident to 911, and was taken to the emergency room. He died approximately 8.5 h post‐ingestion despite treatment. There were no significant findings in the autopsy, the victim's heart blood sample, gastric contents, and the white powder the victim had taken were submitted to the department of forensic toxicology. Using scanning electron microscopy energy dispersive X‐ray analysis, potassium and gold (Au) were detected in the white powder. Ion chromatography analysis detected cyanide. Concentrations of cyanide were 0.5 mg/L in heart blood and 13.3 mg/L in gastric contents. Qualitative and quantitative analyses of Au in the heart blood sample and gastric contents using inductively coupled plasma‐optical emission spectrometry detected concentrations of 79.8 mg/L and 2010.1 mg/L, respectively. Au and cyanide synergistically enhance cytotoxicity through inhibition of detoxification and increasing intracellular accumulation. In the present case, the detected blood cyanide concentration was sub or minimally lethal, and the blood Au concentration was high. The cause of the victim's death was the combined toxicity of Au and cyanide. [ABSTRACT FROM AUTHOR]

Background Method Results Conclusion Approximately 1% of Sweden's 90 000 annual deaths were reported caused by poisoning. In this study, we aim to describe this poisoning population's characteristics, autopsy frequency and results of toxicology testing.A national cohort study based on Swedish national registers. All deceased subjects older than 18 years with poisoning as the cause of death registered between 1 January 2000 and 31 December 2021 were included. Causes of death according to primary ICD‐10 code were analysed along with the substances found in forensic chemistry testing.There were 27 057 poisonous deaths during the study periods 2 018 495 adult deaths. Subjects deceased due to poisoning had a median age of 53 years, and 18 838 (70%) were men. A private home was the most reported location of death (52%). In total, 23 260 (87%) did undergo some sort post‐mortem examination. Drugs (synthetic narcotics, opioids, heroin) caused 12 448 (46%) deaths, and alcohols explained 9056 cases (33%). Positive toxicological tests were found in 22 550 (83%) of the subjects. The most common separate substances were ethanol, zopiclone and nordazepam.Poisoning caused 1.3% of Swedish deaths. Men in their 50s were the most common victims, and their deaths were often cause by synthetic narcotics, other opioids or alcohol. The autopsy frequency was lower than expected for poisonous deaths. [ABSTRACT FROM AUTHOR]

In multidisciplinary science, Analytical approaches based on spike and recovery (SAR) play a substantial role in analytical testing. The spike and recovery method is an important technique for analyzing and accessing the accuracy of analytical methods. The goal of this review seeks to provide clarity on the role of SAR methods in the forensic science discipline. Recent literature has been searched from numerous databases like Google, Web of Sciences, Scopus, PubMed, Google Scholar, and SciFinder. Websites like Science Direct are critically explored to gather scientific reports related to SAR utility. This review discusses the applications and current role of the SAR methods in Forensic Toxicology. It is suggested as one of the major parameters in the validation of the analytical method. SAR methodology is extremely important for the identification and quantitation of analytes in the sample matrix. Moreover, the extension of SAR methods to any scientific discipline is equally important for quality assurance. All relevant processes like method development and its optimization, quality control, and assurance rely on SAR-based studies. However, the method requires better apprehension and needs to be utilized using standard guidelines. [ABSTRACT FROM AUTHOR]

Various samples—including two vials with a pharmaceutical appearance—were submitted to the laboratory for identification. The aim of this work was to describe the unique characteristics observed during the analysis of the powder contained in the vial. Samples were submitted to HPLC‐DAD, UHPLC‐TOF‐MS, and/or UPLC‐MS–MS analysis. The majority of the samples were easily identified as standard drugs of abuse. The main difficulty lay in identifying the powder in the vials. No match was found in the library through HPLC‐DAD analysis. Fortunately, the vials were labeled as "Melanotan II", although the UV spectrum was not available. Mass spectrometric analysis of melanotan II was challenging, as it is a small peptide with a molecular weight of 1024 Da, which is significantly heavier than classical drugs that the laboratory usually handles. As a result, mass spectrometer's parameters can be limited to detect masses up to 1000 Da. Additionally, melanotan II is multi‐charged which is also unusual for compounds typically targeted in our daily work. Finally, the reference standard allowed us to confirm the identification with both instruments, and determine the purity of 30%. Melanotan II is not approved on the market due to safety concerns. It is used illegally mainly for tanning, explaining its nickname "Barbie drug". To conclude, analysis of melanotan II was challenging as it is heavy and doubly charged. Moreover, its UV spectrum was initially not available in the literature. The difficulties faced by forensic scientists in detecting this drug may explain its popularity on the illicit market. [ABSTRACT FROM AUTHOR]

Diester diterpenoid alkaloids (DDAs) are the main active ingredients of herbaceous perennial plants Aconitum. DDAs possess cardiotoxic and neurotoxic properties. Although most deaths caused by DDA poisoning are accidental, a few instances of suicide and homicide have been reported. Presented is a case of an acute aconitine (AC) poisoning following the ingestion of approximately 50 mL of homemade medicinal liquor. We described the clinical manifestations after poisoning and detailed postmortem changes, and detected the concentrations of AC and hypaconitine (HA) by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The decedent experienced a burning sensation in the gastrointestinal tract after poisoning, followed by flushing and paralysis of the face and limbs, and severe cardiac arrhythmia. An autopsy revealed cyanosis of the lips and nail beds; conjunctival hemorrhage in both eyes; pulmonary edema; tissue hemorrhage and congestion in multiple organs; and inflammatory cell infiltration in the stomach, duodenum, pancreas, and cardiac muscle. The concentrations of AC and HA were as follows: cardiac blood, 38.4 ng/mL and 7.1 ng/mL; pericardial fluid, 7.3 ng/mL and 41 ng/mL; urine, 28.1 ng/mL and 574 ng/mL; bile, 38.5 ng/mL and 108 ng/mL; gastric contents, 0.06 mg and 0.56 mg; liver tissue, 10.7 ng/g and 109.6 ng/g; and medicinal liquor, 0.568 mg/mL and 0.664 mg/mL, respectively. The clinical manifestations, anatomy findings, and quantitative data on the concentrations of AC and HA in body fluids and tissues will aid forensic investigations of deaths caused by acute AC poisoning. [ABSTRACT FROM AUTHOR]

The complexity of the drug market and the constant updating of drugs have been challenging issues for drug regulatory authorities. With the emergence of new psychoactive substances (NPS) and the nonmedical use of prescription drugs, forensic and toxicology laboratories have had to adopt new drug screening methods and advanced instrumentation. Using high‐performance liquid chromatography coupled with Orbitrap mass spectrometry, we developed a screening method for common NPS and other drugs. Two milliliters of mixed solvent of n‐hexane and ethyl acetate (1:1, v:v) were added to 500 μL of blood or urine sample for liquid–liquid extraction, and methanol extraction was used for hair samples. The developed method was applied to 3897 samples (including 332 blood samples, 885 urine samples, and 2680 hair samples) taken from drug addicts in a province of China during 2019–2021. For urine and blood samples, the limits of detection (LODs) ranged from 1.68 pg/mL to 10.7 ng/mL. For hair samples, the LODs ranged from 3.30 × 10−5 to 4.21 × 10−3 ng/mg. The matrix effects of urine, blood, and hair samples were in the range of 47.6%–121%, 39.8%–139%, and 6.35%–118%, respectively. And the intra‐day precision was 3.5%–6.0% and the inter‐day precision was 4.18%–9.90%. Analysis of the actual samples showed an overall positive detection rate of 58.9%, with 5.32% of the samples indicating the use of multiple drugs. [ABSTRACT FROM AUTHOR]

For the past decade, illicitly manufactured fentanyl has been a primary contributor in drug overdose deaths regardless of age. The pediatric population is particularly vulnerable to fentanyl exposure, yet there are limited case reports involving this population. Postmortem cases from 2019 to 2023 were retrospectively analyzed to determine the prevalence of fentanyl in decedents between 0 and 12 years of age. Over this time frame, the fentanyl positivity rate increased from 2.6 to 6.2% (n = 632). The most commonly reported age group was 0–4 years, with a peak around 1 year of age for toddlers. Fentanyl concentrations in blood (n = 573) ranged from 0.19 to 360 ng/mL (mean 18 ng/mL, median 6.9 ng/mL). Polydrug use was present in 428 cases; midazolam (n = 96) and methamphetamine (n = 66) were the most common drugs found concurrently in blood with fentanyl, followed by markers of illicitly manufactured fentanyl, such as xylazine (n = 23), para‐fluorofentanyl (n = 18), and acetyl fentanyl (n = 17). This report contrasts the differences in postmortem pediatric fentanyl toxicology results for three groups of case histories: likely medical intervention (n = 113), pregnancy/birth related (n = 136), and inadvertent/intentional exposure (n = 196). Overall, this study provides a retrospective review of postmortem pediatric fentanyl concentrations in a variety of biological matrices and highlights the need for comprehensive toxicology testing in postmortem pediatric casework. [ABSTRACT FROM AUTHOR]

Background: A growing number of studies investigated the factors that contribute to driving under the influence (DUI) of alcohol in relation to gender. However, a gendered approach of the scientific evidence is missing in the literature. To fill this gap, a gender-driven systematic review on real case studies of the last two decades was performed. In addition to the gender of the drivers involved, major independent variables such as the period of recruitment, the type of drivers recruited, and the geographical area where the study was conducted, were examined. Afterwards, a meta-analysis was performed comparing alcohol-positive rates (APR) between male and female drivers in three subgroups of drivers: those involved in road traffic accidents, those randomly tested on the road, and volunteers. Methods: Three databases were searched for eligible studies in October 2023. Real-case studies reporting APR in man and women convicted for DUI of alcohol worldwide were included. Univariate analysis by ANOVA with post-hoc tests identified the independent variables with a significant impact on the dependent variable APR, according to a relationship subsequently investigated by standard multiple linear regression. The meta-analysis of random effects estimates was performed to investigate the change in overall effect size (measured by Cohen's d standardized mean difference test) and 95% confidence interval (CI). Results: Among papers addressing driver gender, univariate analysis of independent variables revealed a higher Alcohol Positive Rate (APR) in men, particularly in drivers involved in crashes, with a noticeable decrease over time. Analyzing the gender of drivers involved in crashes, the meta-analysis showed that men had a significantly higher APR (30.7%; 95%CI 26.8–35.0) compared to women (13.2%; 95%CI 10.7–16.1). However, in drivers randomly tested, there was no significant difference in APR between genders (2.1% for men and 1.4% for women), while in volunteers, there was a statistically significant difference in APR with 3.4% (95%CI 1.5–7.6) for men and 1.1% (95%CI 0.5–2.7) for women. Conclusion: Despite a progressive decrease in the epidemiological prevalence of alcohol-related DUI over time, this phenomenon remains at worryingly high levels among drivers involved in road traffic accidents in both genders, with a higher prevalence in men. It's important for policymakers, professionals, and scientists to consider gender when planning research, analysis, interventions, and policies related to psychoactive substances, such as alcohol or other licit drugs. Forensic sciences can play a vital role in this regard, enabling a thorough analysis of gender gaps in different populations. [ABSTRACT FROM AUTHOR]

Rationale: Tramadol (T) is a strong painkiller drug that belongs to the opioid analgesic group. Several accidental intoxication cases after oral administration of T have been reported in the past decade. Tramadol, its derivatives, and metabolites present information‐limited mass spectra with one prominent peak representing the amine‐containing residue; therefore, their structural determination based on both electron impact mass spectrometry (EI‐MS) and ESI‐MS/MS spectra could be misleading. Methods: A novel analytical method for the structural elucidation of tramadol, its four homologs, and its two main phase I metabolites (N‐desmethyltramadol and O‐desmethyltramadol) was developed using chemical modification and liquid chromatography–high‐resolution tandem mass spectrometry (LC‐HR‐MS/MS) with Orbitrap technology. Results: After chemical derivatization, each of the investigated T series exhibited informative mass spectra that enabled better exposition of their structures. The developed method was successfully implemented to explicitly identify the structures of tramadol and its N‐desmethyltramadol metabolite in urine samples at low ng/mL levels. Conclusions: An efficient derivatization‐aided strategy was developed for rapidly elucidating the structure of tramadol‐like compounds. The method is intended to assist forensic chemists in better diagnosing T and its analogs and metabolites in clinical or forensic toxicology laboratories. [ABSTRACT FROM AUTHOR]

A simple and rapid qualitative chromatographic method with a unique extraction approach was developed and validated to screen oral fluid samples for 31 compounds in driving under the influence of drugs investigations. The scope and sensitivity of the method meets or exceeds Tier I recommendations established by the National Safety Council's Alcohol, Drugs and Impairment Division. Since this is a targeted chromatographic screen (rather than an immunoassay), cutoffs were set to match the confirmation levels in the recommendations. Sample preparation involved a single-step liquid–liquid extraction procedure, using a mixture of methyl tert -butyl ether, isopropanol, and hexane and was applied to samples collected with the Quantisal™ device. Instrument analysis was conducted by liquid chromatography–tandem mass spectrometry, using a Restek Raptor™ biphenyl column for chromatographic separations and a total run time of 8 min. Validation results met all requirements of ANSI/ASB Standard 036 (1st edition)—Standard Practices for Method Validation in Forensic Toxicology. [ABSTRACT FROM AUTHOR]

Liquid chromatography–triple quadrupole mass spectrometry (LC–MS-MS) assays are frequently utilized for screening and confirmatory purposes in the forensic toxicology laboratory. While these techniques are excellent for the targeted identification and quantitation of a wide variety of drug classes, validation and determining fit-for-purpose is a significant requirement for each method. In the USA, the American National Standards Institute and Academy Standards Board first edition of Standard 036 currently serves as a primary resource in forensic toxicology method validation and mandates that laboratories evaluate critical performance characteristics to help ensure the production of forensically defensible results. Due to the variability of specimen quality frequently encountered in the discipline of postmortem toxicology, the State of Maryland Office of the Chief Medical Examiner Forensic Toxicology Laboratory routinely analyzes solid tissue specimens as part of the medicolegal death investigation process and evaluates liver as a representative solid tissue matrix during method validation. Authentic postmortem specimens (e.g. liver, kidney, skeletal muscle, and spleen) were used to investigate the effects of analyzing solid tissue homogenate versus solid tissue supernatant on bias, precision, and ionization suppression/enhancement of Δ9-THC and Δ9-THCCOOH. Bias was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant with a single exception of the low QC concentration for Δ9-THC in liver homogenate (–29%). Within-run and between-run CV was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant. Δ9-THC and Δ9-THC-d3 exhibited significant ion suppression in both liver homogenate and supernatant, while Δ9-THCCOOH and Δ9-THCCOOH-d3 showed both ion suppression and enhancement in these matrices. Noticeable quantitative differences were observed in authentic postmortem solid tissue homogenate and supernatant specimens despite evaluating identical tissue samplings. A brief discussion of the results is presented using a validated LC–MS-MS method for the confirmation and quantitation of Δ9-THC and Δ9-THCCOOH in postmortem casework. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids emerged in the early 21st century and have continued to evolve and flourish to present day. Like other novel psychoactive substances (NPS), synthetic cannabinoids have been sold under the guise of legitimate products. Some examples include "potpourri," "incense," and herbal material. Between May 2020 and December 2023, the United States Army Criminal Investigation Laboratory, Drug Chemistry Division (USACIL) received 29 seized drug cases mentioning "blue lotus" or "valerian root." In 90% of these cases, at least one exhibit contained one or more synthetic cannabinoids. During the same timeframe, the Armed Forces Medical Examiner System, Division of Forensic Toxicology received 65 toxicology cases that contained synthetic cannabinoids and/or their corresponding metabolites where case history mentioned "blue lotus." The most frequently observed synthetic cannabinoids between laboratories were 5F-MDMB-PICA, ADB-BUTINACA, and MDMB-4en-PINACA. Innocuous branding and marketing may deceive law enforcement, investigators, and healthcare providers into believing that the adverse effects of erratic behavior, sedation, slurred speech, and hallucinations are a result of toxicity from botanical extracts (e.g. apomorphine and nuciferine in blue lotus). Due to the dangerous nature of these NPS, synthetic cannabinoid screening is recommended for all cases where there is suspected use of vaping products suggested to contain "blue lotus" or "valerian root" as vendors continue to conceal the presence of these compounds. [ABSTRACT FROM AUTHOR]

For the past 60 years, benzodiazepines such as chlordiazepoxide, diazepam, and alprazolam have been used as pharmaceutical medications for the treatment of myriad conditions including anxiety, seizures, and insomnia. In more recent years, novel benzodiazepine derivatives have emerged as illicit substances in powders and counterfeit tablets on the illicit drug market. In 2016, bromazolam, a brominated derivative of alprazolam, emerged on the illicit drug market in Europe, but the substance was not reported in the USA until 2019–2020. In this study, we report the emergence and subsequent prevalence of bromazolam in postmortem blood in the state of Indiana during 2023. Analysis was completed by a solvent protein precipitation extraction with acetonitrile and detection by liquid chromatography with quadrupole time of flight mass spectrometry. During 2023, bromazolam was detected in 94 cases across 25 counties in Indiana. It was never the sole substance detected and was commonly detected alongside fentanyl (83 cases), norfentanyl (77 cases), 4-anilino- N -phenethylpiperidine (76 cases), acetylfentanyl (49 cases), methamphetamine (32 cases), naloxone (25 cases), 11-nor-9-carboxy-tetrahydrocannabinol (24 cases), and benzoylecgonine (20 cases). After official query with the Indiana Department of Health, it was found that bromazolam was specifically included in the cause of death certification in 31 fatalities (32.9%). Due to the scarcity of information regarding this novel benzodiazepine derivative in postmortem toxicology and its involvement in fatalities, it is important that forensic toxicology laboratories consider adding bromazolam to their comprehensive scope of analysis. [ABSTRACT FROM AUTHOR]

Background: Medico-legal cases in a particular health set up is an important and unavoidable bulk. It requires proper dealing in both examination and documentation. Classification and tabulation of these cases under certain categories is crucial for evaluating the current pattern. This categorisation benefits the law-and-order authorities to enact norms and policies accordingly. Methods: This is a retrospective study conducted at Rohilkhand Medical College and Hospital, Bareilly by the department of Forensic Medicine & Toxicology in collaboration with the Medical Record Section. Medico-Legal Cases examined by doctors attending in the casualty of the hospital were taken. Medico-legal case file and electronic medical record data saved in the (MRD) medical records department were looked for cases segregated as Medico-Legal Cases with Medico-Legal Reports for a duration of one year from 01-July-2023 to 30-June-2024.Both percentage and numbers of the evaluated data are mentioned. Results: Total 456 cases were reported during 01-July-2023 to 30-June-2024. Among the 456 cases reported, 32.00% were among the age group of 21-30 years. Most of the medicolegal cases registered were of males (73.50 %). The number of cases from rural areas were more (73.00%). Road Traffic accidents (RTA) accounted for 64.70% of the cases followed by poisoning/drug reaction cases (13.20%). Among the RTA cases, the age group of 21-30 years were the most vulnerable. Conclusion: Evaluation of the Medico-legal Cases needs focused observation and meticulous recording with proper documentation. Heath care staffs including doctors should undergo proper training so that the faults and mistakes can be minimised, thus aiding the legal authorities to manage this bulk efficiently. [ABSTRACT FROM AUTHOR]

Betablockers are one of the most frequently used medications in cardiology. They can lead to fatal drops in blood pressure and heart rhythm disturbances. Death is functional, and poisoning with this group of drugs can be difficult to detect. The liquid–liquid extraction (LLE) method developed using ethyl acetate at pH 9 successfully identified 18 β-blockers in human blood. The method's limit of quantification (LOQ) was in the range of 0.1 to 0.5 ng/mL. No carryover of substances between samples was detected, and no interfering ion current signals were observed in the biological samples at the retention times of the compounds or internal standards. All compounds had a coefficient of determination (R2) above 0.995. Intraday and interday precision (RSD%) and accuracy (RE%) for low and high QC levels were within 1.7–12.3% and −14.4 to 14.1%, respectively. Very good recovery (80.0–119.6%) and matrix effect (±20.0%) values were achieved for all compounds. In addition, fragmentation spectra were collected for all the examined substances, and high-resolution spectra were presented for landiolol and metipranolol, because they are not available in commercial HRMS spectra databases. The developed method was applied in authentic postmortem samples. [ABSTRACT FROM AUTHOR]

A multi‐analyte liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method is described, involving the separation of delta‐9‐tetrahydrocannabinol (delta‐9‐THC) and delta‐8‐THC in addition to other commonly encountered drugs and metabolites. Briefly, sample preparation involved an alkaline liquid–liquid extraction (methyl tert‐butyl ether) of blood (100 μl). The solvent layer was transferred, evaporated to dryness, reconstituted, and samples then separated on an Agilent Poroshell 120 EC‐C18 100 Å (50 mm × 3.0 mm, 2.7 μm) analytical column using a multi‐step gradient elution of 50 mM ammonium formate in water (pH 3.5) and 0.1% formic acid in methanol over 14 min. A SCIEX Triple Quad 6500+ system operating in scheduled multiple reaction monitoring and positive electrospray ionization was used for detection. There were no interferences, and matrix effects were generally acceptable (±20% of neat response). Linearity was achieved within the calibration range, including methylamphetamine (MA) (10–1000 ng/ml), 3,4‐methylenedioxy‐N‐methylamphetamine (MDMA) (10–1,000 ng/ml), cocaine (10–1000 ng/ml), and two THC isomers (1–100 ng/ml). Accuracies of MA, MDMA, cocaine, and two THC isomers were 3.6 to 8.9%, −1.2 to 4%, −5.3 to 5.8%, and −11 to 14%, respectively; while precision estimates of the same were 1.6 to 5.4%, 1.7 to 5.3%, 1.2 to 4.5%, and 2 to 10%, respectively. Autosampler stability and dilution integrity were within acceptable limits, and no carryover was detected at the limit of detection. This validated LC‐MS/MS method made the routine identification of both delta‐9‐THC and delta‐8‐THC in blood possible. [ABSTRACT FROM AUTHOR]

Drowning remains a significant cause of mortality worldwide, necessitating accurate diagnostic tools for forensic investigation. This paper conducts a comparative analysis of the Drowning Index (DI) to ascertain its relevance in distinguishing drowning deaths from non-drowning asphyxial deaths. Drowning deaths present a challenge for forensic pathologists, because the autopsy findings may occur in many non-drowning scenarios. Previous studies have attempted to identify patterns in organ weights that may be specific for drowning. The drowning index has been defined as the weight ratio of the lungs and pleural effusion fluid to the spleen. We compared the lung and pleural effusion weight, spleen weight, and DI from 124 autopsies of asphyxia deaths including both drowning deaths and non-drowning asphyxia deaths such as hanging, strangulation, suffocation and mechanical asphyxia at the department of Forensic Medicine and Toxicology at the Gandhi Medical College, Bhopal from September 2021 to August 2022. Findings highlight the potential utility of the DI as a valuable adjunctive tool in forensic investigations, providing insights into its comparative efficacy in differentiating drowning from other modes of asphyxial deaths. Such insights are critical for enhancing accuracy in forensic diagnoses and contributing to advancements in medicolegal death investigations. [ABSTRACT FROM AUTHOR]

Introduction: Medico legal deaths including burns claim a substantial number of lives in central Karnataka. 'A prospective Study of Histo-Pathological changes in Lungs, Liver and Kidneys in Burns Cases' was carried out at the Department of Forensic Medicine & Toxicology, SS hospital, SSIMS & RC, Davangere. Material & methods: The present study was carried out for the period of 3 years from January 2021 to December 2023. Totally 100 cases with burns and scalds injuries brought to the mortuary for autopsy was the material for study and collection of tissues for histopathological examination. Observations & Results: In the present study, histopathological changes in lungs showed congestion, pulmonary edema, Diffuse alveolar damage or ARDS changes, bronchopneumonia, interstitial pneumonitis, anthracotic pigment, carbon laden macrophages, intravascular thrombi, septic emboli, interstitial & intra alveolar hemorrhage. Histopathological changes in liver showed congestion, fatty change, centrilobular necrosis, cloudy swelling, focal hemorrhage, necrosis, portal inflammation. Histopathological changes in kidneys showed ATN in majority of cases, cloudy degeneration, congestion, tubularcasts and acute pyelonephritis in rest of the cases. Conclusion: The effect of burns on vital organs can be assessed through histopathological examination, which helps in determining the post burn complications and which aid in better treatment outcome of the burn's patients. [ABSTRACT FROM AUTHOR]

Ethanol is the most commonly encountered substance in forensic toxicology. Determining blood alcohol concentration (BAC) in autopsies accounts for the majority of work in forensic diagnosis. The most common method to assess BAC is the enzymatic oxidation method because of its low cost, easy operation, and high throughput. Still, the elevated lactate and lactate dehydrogenase (LDH) levels in postmortem blood may affect accuracy. This study uses headspace gas chromatography with a flame ionization detector (HS-GC/FID) to assess the interference of lactate and LDH levels on BAC in 110 autopsied blood samples determined by the enzymatic oxidation method. The results showed that lactate and LDH levels in postmortem blood were higher than in normal blood. There was a weak correlation between the lactate levels and BAC difference (r = 0.23, p < 0.05) and a strong correlation between LDH levels and BAC difference (r = 0.67, p < 0.001). The differentiation of BAC between the enzymatic oxidation method and HS-GC/FID was significant (p < 0.001), confirming the interference significantly. All postmortem blood samples with lactate and LDH levels higher than regular lead to a positive error in determining BAC by enzymatic oxidation method. The study results suggest that the HS-GC/FID method should be used to determine BAC in postmortem blood samples instead of the enzymatic oxidation method to avoid mistakes in forensic diagnosis. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is a powerful toxic gas in workplace incidents, and it poses a threat to colleagues or family members involved in rescues, leading to a "domino effect" of multiple deaths. In this report, we describe three incidents in which 10 people died, and we present the results of the analyses performed in different incidents, including paper pulp pit, sewer, and sewage well. We provide the macroscopic and morphological findings of ten victims, which include conjunctival hemorrhage, corneal erosion, pulmonary edema, and pulmonary hemorrhage. Additionally, we observed large amounts of waste paper pulp or black sludge in the upper and lower respiratory tracts or upper and lower gastrointestinal tracts of six victims. Furthermore, we conducted a toxicological examination of the victims' blood sulfide using an alkylation extraction approach combined with gas chromatography/mass spectrometry. The sulfide concentrations in the 10 victims ranged from 0.06 to 6.72 mg/L. [ABSTRACT FROM AUTHOR]

A retrospective observational study of Victorian deaths involving MA between 2010 and 2019 was conducted to determine the prevalence and contribution of methylamphetamine (MA) toxicity to death in the absence of other factors. Demographics, autopsy findings, toxicology, and the cause of death were reviewed. Coronial cases were categorized into five groups: deaths due to MA toxicity in the absence of other factors (Group A1); deaths due to MA toxicity in the setting of other potentially contributing factors (Group A2); deaths due to MA toxicity in the setting of significant natural disease (Group B); deaths primarily due to multiple-drug toxicity (Group C); and deaths primarily due to natural causes (Group D). There were 506 deaths involving MA categorized into Group A1 (n = 1, 0.6%), Group A2 (n = 8, 1.6%), Group B (n = 28, 5.5%), Group C (n = 229, 45%), and Group D (n = 240, 47%). Significant natural disease was prevalent among deaths involving MA and mainly concerned forms of cardiovascular disease (n = 277, 55%). The MA concentration in the one death included in Group A1 was 2.1 mg/L. The median MA concentrations of Group A2 (1.6 mg/L) and Group B (0.5 mg/L) were significantly higher than Group C (0.2 mg/L) and Group D (0.2 mg/L). Additionally, many other toxicologically significant drugs were detected and mostly comprised of central nervous system depressants. Deaths due to MA toxicity in the absence of other factors were rare despite the greater availability of crystal MA in the Australian community. The study highlights the interpretative challenges of MA blood concentrations and the continuing harms of this drug in Australia. [ABSTRACT FROM AUTHOR]

Young individuals constitute an intriguing population, as their drinking habits are notably shaped by their perception of their peers' alcohol consumption. Nonetheless, excessive alcohol intake can have detrimental effects on academic performance, interpersonal relationships, and the risk and severity of accidents. This study reported the first data involving students enrolled from three universities on a voluntary basis for alcohol consumption evaluation. Alcohol consumption was assessed through questionnaires and EtG quantification in hair (hEtG) carried out by liquid chromatography-mass spectrometry (LC–MS/MS) analysis after a solid-phase extraction (SPE) purification step. The results of our study demonstrated that 77.1% of samples tested negative for hEtG or displayed hEtG ≤ 5 pg/mg. Particularly, the student population was not characterized by samples with hEtG indicative of chronic excessive consumption (hEtG ≥ 30 pg/mg). No significant association was identified between biological sex, among the degree course/the year attended, nor in relation to BMI or smoking/coffee consumption. Among the obtained results, it was worth noting that the comparison of self-reporting abstinence from tobacco and coffee accounted for 65.3% and 16.7%, respectively, while only 2.8% of the total declared abstinence from alcohol. The current study has uncovered a significant level of interest among students in this analysis and its interpretation. This suggests that implementing public health promotion activities within a university setting could be beneficial. [ABSTRACT FROM AUTHOR]

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

Sodium nitrite (NaNO2) is an inorganic compound that is commonly used as a preservative (E250) in the fish and meat industry. When ingested, sodium nitrite will lead to methemoglobinemia, hypotension, and arrhythmias. An increasing trend in the use of sodium nitrite as a suicide agent has been reported. In Belgium however it remains a rare phenomenon. The ingestion of sodium nitrite is not always apparent from the death scene investigation, especially in cases of covert administration or accidental ingestion. Hence, the forensic pathologist must be aware of this trend and the postmortem changes related to the ingestion of sodium nitrite to effectively identify these cases and determine the cause and manner of death. We describe a case of fatal self-poisoning following the oral ingestion of sodium nitrite with suicidal intent. Postmortem investigations showed signs of methemoglobinemia, such as a gray-brown discoloration of lividity and a chocolate brown discoloration of the blood. Postmortem toxicological investigation revealed methemoglobinemia (35%) in cardiac blood, hypernatremia (159.6 mmol/L) in vitreous humor, and the presence of nitrite in gastric contents (1.15 g/L) and, for the first time in a forensic case, in serum (38 µg/mL). A review of the existing literature regarding cases of sodium nitrite intoxications was performed to correlate these findings. [ABSTRACT FROM AUTHOR]

A variety of LSD analogs have emerged in recent years with dual purposes of avoiding prosecution from possession while providing new options for those willing to experiment with hallucinogenic drugs. In this study, a previously published automated sample preparation method for LSD and its primary metabolite (OH‐LSD) was utilized to extract LSD, OH‐LSD, and nine LSD analogs from urine. The liquid chromatography tandem mass spectrometry (LC–MS/MS) method was modified from the previously published LC conditions to utilize a different analytical column and gradient elution program. Mobile phases of 10 mM ammonium formate with 0.1% formic acid in deionized water (mobile phase A) and 0.1% formic acid in methanol (mobile phase B) were employed. The method was validated to ANSI/ASB Standard 036 with a 0.1 ng/mL limit of detection for all analytes and was utilized for the analysis of 325 urine specimens. Although no LSD analogs were observed in the samples analyzed, this validated method was demonstrated to be suitable for the analysis of these compounds in laboratories seeking to expand their testing scope. Automated sample preparation allows for the efficient analysis of these analytically challenging compounds with minimal manual handling. Additionally, there was no increased analytical time burden when the LC column and gradient were modified to target nine additional analytes. Detection may improve as new reference standards are developed to allow laboratories to focus on the metabolic products of these analogs. For now, this validated procedure can assist with the routine analysis and surveillance of these emerging substances. [ABSTRACT FROM AUTHOR]

When faced with increasing drug‐related deaths and decline in practicing forensic pathologists, the need to quickly identify toxicology‐related deaths is evident in order to appropriately triage cases and expedite turnaround times. Lateral flow immunoassays conducted pre‐autopsy offer quick urine drug screen (UDS) results in minutes and are used to inform the need for autopsy. Over 1000 medicolegal cases were reviewed to compare UDS results to laboratory enzyme‐linked immunosorbent assay (ELISA) blood results to evaluate how well autopsy UDS predicted laboratory findings. Mass spectral analysis was performed on ELISA‐positive specimens and these data were used to investigate UDS false‐negative (FN) results when possible. Five different UDS devices (STAT One Step Drug of Abuse dip card and cassette, Premiere Biotech multi‐drug and fentanyl dip cards and ATTEST 6‐acetylmorphine (6‐AM) dip card) were tested encompassing 11 drug classes: 6‐AM, amphetamine/methamphetamine, benzodiazepines, benzoylecgonine, fentanyl, methadone, opioids, phencyclidine, and delta‐9‐tetrahydrocannabinol. Sensitivity, specificity, efficiency, and positive and negative predictive values >80% indicated that UDS was useful for predicting cases involving benzoylecgonine, methadone, methamphetamine, and phencyclidine. UDS was unreliable in predicting amphetamine, benzodiazepines, fentanyl, and opiates‐related cases due to a high percentage of FN (up to 11.2%, 8.0%, 12.4%, and 5.5%, respectively) when compared to ELISA blood results. For the later analytes, sensitivities were as low as 57.5%, 60.0%, 72.2%, and 66.7%, respectively. Overall results support that UDS cannot replace laboratory testing. Because UDS is subject to false‐positive and FN results users must understand the limitations of using UDS for triage or decision‐making purposes. [ABSTRACT FROM AUTHOR]

Novel synthetic opioids (NSOs) represent an emerging group of novel psychoactive substances, acting as agonists at the opioid receptors. NSOs include fentanyl-related compounds, e.g. methoxyacetylfentanyl (MeACF), and non-fentanyl analogs, e.g. "U compounds" including U-47700. Here we present three cases of death involving MeACF and U-47700, with particular reference to preliminary data on pharmacokinetics and tissue distribution. After a complete post-mortem examination, general unknown screenings and analysis of drugs of abuse were performed on postmortem samples by immunoassays, gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry. To quantify the analytes of interest in post-mortem blood and tissues, the standard addition method was used. A toxicological significance score (TSS), weighing the role of the NSO in each death case, was assigned. Case 1 died at the hospital after consumption of U-47700, methadone (serum levels: 2,600 ng/ml and 37 ng/ml), tilidine and benzodiazepines. In case 2, U-47700 (204 ng/ml) together with methadone (290 ng/ml), flubromazepam (480 ng/ml) and diazepam (300 ng/ml) were detected in peripheral blood. In case 3, methoxyacetylfentanyl (266 ng/ml), furanylfentanyl (4.3 ng/ml) 4-ANPP (15 ng/ml) and alprazolam (69 ng/ml) were quantified in femoral blood. In all cases, the NSO likely contributed to the death (TSS = 3). NSOs appear to be often consumed in the setting of polydrug intoxications, especially in combination with other opioids and benzodiazepines, which often exert synergistic effects. The standard addition method remains the most reliable in post-mortem analysis and toxicological results should always be evaluated together with circumstantial and autopsy data. [ABSTRACT FROM AUTHOR]

2-Benzylbenzimidazole 'nitazene' opioids are presenting a growing threat to public health. Although various nitazenes were previously studied, systematic comparisons of the effects of different structural modifications to the 2-benzylbenzimidazole core structure on μ-opioid receptor (MOR) activity are limited. Here, we assessed in vitro structure–activity relationships of 9 previously uncharacterized nitazenes alongside known structural analogues. Specifically, we focused on MOR activation by 'ring' substituted analogues (i.e., N-pyrrolidino and N-piperidinyl modifications), 'desnitazene' analogues (lacking the 5-nitro group), and N-desethyl analogues. The results from two in vitro MOR activation assays (β-arrestin 2 recruitment and inhibition of cAMP accumulation) showed that 'ring' modifications overall yield highly active drugs. With the exception of 4′-OH analogues (which are metabolites), N-pyrrolidino substitutions were generally more favorable for MOR activation than N-piperidine substitutions. Furthermore, removal of the 5-nitro group on the benzimidazole ring consistently caused a pronounced decrease in potency. The N-desethyl modifications showed important MOR activity, and generally resulted in a slightly lowered potency than comparator nitazenes. Intriguingly, N-desethyl isotonitazene was the exception and was consistently more potent than isotonitazene. Complementing the in vitro findings and demonstrating the high harm potential associated with many of these compounds, we describe 85 forensic cases from North America and the United Kingdom involving etodesnitazene, N-desethyl etonitazene, N-desethyl isotonitazene, N-pyrrolidino metonitazene, and N-pyrrolidino protonitazene. The low-to-sub ng/mL blood concentrations observed in most cases underscore the drugs' high potencies. Taken together, by bridging pharmacology and case data, this study may aid to increase awareness and guide legislative and public health efforts. [ABSTRACT FROM AUTHOR]

In forensic toxicology, the pediatric population requires special focus when evaluating positive findings because of the many toxicokinetic and toxicodynamic differences (e.g. metabolic capabilities, body size, etc.) between the pediatric and adult populations. In particular, the administration of over-the-counter (OTC) medications needs careful consideration, as dosages given to the pediatric population (0 days–18 years), particularly those given to individuals <5 years of age, tend to be lower than those given to individuals closer to adulthood. Postmortem pediatric data from 11 years (2010–2020) was compiled. A total of 1413 positive cases contained one or more of the following common OTC medications: antihistamines (brompheniramine, chlorpheniramine, diphenhydramine, doxylamine and pheniramine), pain relievers (acetaminophen, naproxen, ibuprofen and salicylates), cold/flu medications (dextro/levomethorphan, guaifenesin, ephedrine and pseudoephedrine), gastrointestinal aids (dicyclomine and loperamide) and/or sleep aids (melatonin). Antihistamines, cold/flu medications and pain relievers are the most common classes of drugs encountered in the postmortem pediatric population. To evaluate trends, three main age groups were created: ≤5 years old (5 U, birth-5 years old), middle childhood (MC, 6–11 years old), and early adolescence (EA, 12–18 years old). When considering the data, it must be noted that many of these drugs may be co-administered in single and/or multi-drug formulations. In addition, some drugs may have a variety of uses, e.g. antihistamines may also be used as sleep aids. Of note, the prevalence of cases involving those aged 6–11 years old was far less than their younger and older pediatric counterparts. With the widespread availability of OTC medications, unintentional overdoses, recreational misuse and suicidal overdoses can occur in the vulnerable, pediatric population. [ABSTRACT FROM AUTHOR]

• Retrograde calculations in the UK do not provide a 99.7% confidence interval. • Back calculations should only be permitted 2 h after cessation of drinking. • A elimination range of 8–29 mg% provides coverage at the 99.7 % confidence level. • Emphasis in expert reports on most likely elimination range should be removed. Retrograde extrapolations, known as back calculations are widely used in forensic toxicology to estimate the blood alcohol concentration of an individual at some prior time. In the UK guidelines have been issued by the United Kingdom and Ireland Association of Forensic Toxicologists) and the Organization of Scientific Area Committees (OSAC) for Forensic Science. However, these guidelines are not fully agreed and open to interpretation. Alcohol elimination rates have been discussed in numerous publications since Widmark's original data was published. The current guidance from UKIAFT, is to report the most likely back calculated result together with a range of results based on the 95% confidence limit elimination rates (9 to 29 mg/100 mL/hour). The Divisional Court, upheld by the House of Lords, ruled that in order to convict someone for being over the prescribed limit on the basis of any back calculation, the case must be proven beyond reasonable doubt. A 99.73% confidence interval increased to 3 standard deviations at the lower end would provide a greater factual basis for the court and cover a larger proportion of the population, this can be achieved by increasing the elimination range to 8 to 29 mg/100 mL/hour. Retrograde extrapolations also rely on the subject being post absorptive at the prior time. In the UK, back calculations are valid if the subject has not eaten or consumed alcohol within one hour of the back calculation time. Where the subject has eaten prior to the back calculation, experts are instructed to consider whether the back calculation is applicable. In Germany and the United States back calculations are not permitted to a time within 2 h after last drink consumed. The 2 h limit would better meet the highest standard of 'beyond reasonable doubt' burden of proof, and should be used. These proposed changes would decrease the uncertainty associated with retrograde calculations carried out by UK toxicologists. [ABSTRACT FROM AUTHOR]

Ethanol blood analysis is the most common request in forensic toxicology, and some studies point to positive results in approximately one-third of all unnatural deaths. However, distinguishing sober deaths from drunk deaths is not as simple as it may seem. This technical, clinical, and forensic interpretation is proposed to interpret the ethanol toxicological results, discussing several artefacts and pitfalls that must be considered, namely focusing on driving under the influence. This work is presented with a practical and objective approach, aiming to alleviate the complexities associated with clinical, physiological, pathophysiological, and toxicological aspects to enhance comprehension, practicality, and applicability of its content, especially to courts. Particularly the physical integrity of the body, the postmortem interval, putrefactive signs, anatomic place of blood collection, alternative samples such as vitreous humour and urine, the possibility of postmortem redistribution, the inclusion of preservatives in containers, and optimal temperature conditions of shipment are among some of the aspects to pay attention. Although several biomarkers related to postmortem microbial ethanol production have been proposed, their translation into forensic routine is slow to be implemented due to the uncertainties of their application and analytical difficulties. Specifically, in the interpretation of ethanol toxicological results, "not everything that can be counted counts and not everything that counts can be counted" (attributed to Albert Einstein). [ABSTRACT FROM AUTHOR]

Fire deaths present several diagnostic challenges for the forensic examiner, the most significant of which is the identification of the cause of death and the evaluation of the morphological consequences of heat injuries in the ante-mortem and post-mortem periods. Here, we describe the case of two young lovers found dead inside a travelling carousel destroyed by a fire. Circumstantial evidence of disputes between families running the town fair raised the suspicion of intentional arson. Comparative analysis of crime scene investigation, radiological, autoptic, histological, and toxicological findings revealed signs of vitality (i.e., presence of soot deposits inside the respiratory and digestive tracts, heat damage to the respiratory mucosa) and identified fatal asphyxia from haemorrhagic pulmonary oedema as the cause of death. Since the experimental burning of plastic samples collected from a similar carousel demonstrated the significant production of phosgene, the death of the two lovers was attributed to the probable inhalation of this gas. The case presented here underlines the importance of a multidisciplinary approach of any fire-related death, providing an insight into circumstantial and forensic (autopsy, toxicological, and immunohistopathological) elements useful in raising suspicion of possible toxic gas inhalation. In the presence of high levels of PVC materials at the fire scene and pulmonary oedema at the autopsy, with no alternative causes of death, the forensic pathologist must suspect a fatal exposure to phosgene. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances (NPS) and new structural scaffolds have emerged on the recreational drug market since the enactment of Chinese SCRA analog controls in 2021. This study reports the first SCRAs to be detected with a bromide at the 5 position (5′Br) on the phenyl ring of the indazole core and without a tail moiety. ADB‐5′Br‐INACA (ADMB‐5′Br‐INACA) and MDMB‐5′Br‐INACA were detected in seized samples from Scottish prisons, Belgian customs, and US forensic casework. The brominated analog with a tail moiety, ADB‐5′Br‐BUTINACA (ADMB‐5′Br‐BUTINACA), was also detected in Scottish prisons and US forensic casework. The metabolites of these compounds and the predicted compound MDMB‐5′Br‐BUTINACA were identified through incubation with primary human hepatocytes to aid in their toxicological identification. The bromide on the indazole remains intact on metabolites, allowing these compounds to be easily distinguished in toxicological samples from their non‐brominated analogs. Glucuronidation was more common for tail‐less analogs than their butyl tail‐containing counterparts. Forensic toxicologists are advised to update their analytical methods with the characteristic ions for these compounds, as well as their anticipated urinary markers: amide hydrolysis and monoOH at tert‐butyl metabolites (after β‐glucuronidase treatment) for ADB‐5′Br‐INACA; monoOH at tert‐butyl and amide hydrolysis metabolites for ADB‐5′Br‐BUTINACA; and ester hydrolysis metabolites with additional metabolites for MDMB‐5′Br‐INACA and MDMB‐5′Br‐BUTINACA. Toxicologists should remain vigilant to the emergence of new SCRAs with halogenation of the indazole core and tail‐less analogs, which have already started to emerge. [ABSTRACT FROM AUTHOR]

Nitrite/nitrate poisoning is an emerging problem, with an ongoing escalation of reported self-administration with suicidal intent in several countries. Nitrites toxicity mainly consists of their interaction with hemoglobin (Hb), causing its oxidization to methemoglobin (MetHb). In order to give support to the correct procedures for the analysis of these cases, this study aims to evaluate spontaneous sample degradation and consequent MetHb formation in the typical storage conditions of a forensic toxicology laboratory. Two different types of samples have been used in this study: the first stage of our study consisted of a retrospective analysis of blood samples obtained by judicial autopsies already stored in the toxicology laboratory, collected over four years (2018–2021), while the samples used for the second stage were appositely collected during judicial autopsies. The data obtained by the application of a derivative spectrophotometry method on these samples suggest that there seems not to be a maximum threshold for MetHb formation within which it is possible to state with a sufficient grade of certainty that the concentration of MetHb found is consistent with an ante-mortem formation and is not the result of an artifact due to sample degradation and storage conditions. On the other hand, the results suggest that MetHb formation depends on the time passed between sample collection and analysis, so that a tempestive sample processing, performed as soon as the samples are received in the laboratory, is crucial to obtain the maximum reliability and diagnostic values from the data when MetHb quantitation is necessary. [ABSTRACT FROM AUTHOR]

The herbicide paraquat (PQ) is responsible for a significant number of fatalities resulting from self-poisoning. Nevertheless, only a limited number of comprehensive studies focusing on fatal PQ poisoning, which include examination of autopsy findings, histopathology, and quantitative analysis of post-mortem samples, have been published. This study aimed to evaluate autopsy findings, histopathology, and quantitative analysis of PQ in post-mortem human serum samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a simple, sensitive, and specific method. Autopsies were performed on all deaths due to PQ poisoning, and serum samples were sent to the toxicology laboratory for chemical analysis. The method was successfully applied to seven human serum samples, and the results indicate its reliability for detecting PQ. The study reports fatal serum PQ levels ranging from 0.5 to 372.0 µg/mL. The comprehensive data presented in this study can be useful for further research and practical applications. [ABSTRACT FROM AUTHOR]

Background: The abuse of psychoactive substances presents challenges in clinical and forensic toxicology. The emergence of novel and potent drugs that pose significant health risks, in particular towards frequent abusers and users unaware of the ingredients, further complicates the situation. Designer benzodiazepines have become a fast-growing subgroup of these new psychoactive substances (NPSs), and their overdose may potentially turn fatal, especially when combined with other central nervous system depressants. In 2021, flubrotizolam, a potent thieno-triazolo designer benzodiazepine, emerged on the illicit market, available online as a "research chemical". The identification of markers of consumption for this designer benzodiazepine is essential in analytical toxicology, especially in clinical and forensic cases. Methods: We therefore aimed to identify biomarkers of flubrotizolam uptake in ten-donor-pooled human hepatocytes, applying liquid chromatography high-resolution mass spectrometry and software-aided data mining supported by in silico prediction tools. Results: Prediction studies resulted in 10 and 13 first- and second-generation metabolites, respectively, mainly transformed through hydroxylation and sulfation, methylation, and glucuronidation reactions. We identified six metabolites after 3 h human hepatocyte incubation: two hydroxylated metabolites (α- and 6-hydroxy-flubrotizolam), two 6-hydroxy-glucuronides, a reduced-hydroxy-N-glucuronide, and an N-glucuronide. Conclusions: We suggest detecting flubrotizolam and its hydroxylated metabolites as markers of consumption after the glucuronide hydrolysis of biological samples. The results are consistent with the in vivo metabolism of brotizolam, a medically used benzodiazepine and a chloro-phenyl analog of flubrotizolam. [ABSTRACT FROM AUTHOR]

Background: Paraquat is a widely used herbicide that raises a significant public health concern due to its extreme toxicity even at low doses and its potential for criminal poisoning. However, most of the research is concentrated on pulmonary toxicity of the compound so far, ignoring its other systemic effects. Moreover, a perfect antidote for this poisoning remains still at large. Case Presentation: In this case report, we present probably the first case of criminal paraquat poisoning in India, involving a 40-year-old man who was poisoned by family members with paraquat-laced alcohol. Although the patient initially appeared to be recovering, his condition worsened, and he died from multi-organ dysfunction syndrome (MODS). Discussion: Paraquat poisoning presents with a spectrum of clinical features, mainly affecting the lungs and kidneys, often leading to respiratory and renal failure. However, its toxicity extends to other organs like liver causing toxic hepatitis that prompts us for a proper diagnosis and management. Current research and management protocols tend to neglect the hepatic and renal toxicities, focusing primarily on pulmonary fibrosis. The manufacture and sale of paraquat in India needs to be reviewed in the light of increasing global bans of this compound. There is also a pressing need for antidote research in dealing with agrochemical substance abuse, particularly paraquat. Conclusion: The emergence of paraquat as a lethal homicidal poison highlights the need for stringent regulations and proactive measures to safeguard public health. The whole saga of chemical/pesticide regulation in our country is very naïve when compared to the global standard. It is time to foster collaboration between regulatory bodies, healthcare professionals, and researchers to address the menace of ‘paraquat deaths’ in India.

Background: Didactic teaching being teacher centric usually does not generate sense of responsibility for learning among the students. The Jigsaw method is a form of cooperative learning that improves not only the cognitive but also the affective and psychomotor skills, which are required by a student to become an Indian Medical Graduate. Thus, this study was aimed at assessing the effectiveness of Jigsaw strategy in comparison to didactic teaching and to understand the perception of the students. Methodology: This was a quasi-experimental study conducted among second year MBBS students. They were randomly assigned to lecture and Jigsaw groups. A topic on general toxicology was chosen. Handouts were prepared which were given to all the students. The lecture group was taught using audio visual aids. The topic was sub divided into five subtopics for Jigsaw group. A post test consisting of MCQs was used to assess the effectiveness of the method. A validated questionnaire was used to gather feedback from the students belonging to Jigsaw Group. Descriptive statistics were used to analyze responses to the Likert scale questions. Results: The present study included a total of 65 II year MBBS students, out of which 30 students were in Jigsaw group. A total of 94% students agreed to participate actively in the Jigsaw session. Most of the students (93%) students listened to and respected the ideas of their peers. A total of 72% students found this method of learning useful in Forensic Medicine and Toxicology. Only 53% of the students felt that the time for preparation and presentation of the topic was sufficient. Conclusions: The present study advocates this cooperating learning method to be an effective tool in better understanding of the subject, to improve communication skills and to inculcate lifelong learning attitude among the medical graduates. The jigsaw method, however, requires more time for planning and execution, to yield positive outcomes.

Both postmortem toxicological and medical-forensic examinations are very important in the case of analyzing various types of chemical substances. Hydroxyzine (HZ) is a first-generation antihistamine drug with a sedative effect that disrupts cognitive function and affects the ability to drive motor vehicles. Enzymatic oxidation of the hydroxy-methyl group to the carboxyl group leads to the formation of its main metabolite—cetirizine (CZ). CZ is the active substance of antiallergic drugs. Because it does not cross the BBB (blood–brain barrier) easily, it is less likely to cause drowsiness or affect memory and impair cognitive function. Therefore, in criminal studies, it is often important what medication had been taken by a person involved, e.g., in a car accident, HZ or CZ. The analysis of both antihistamine drugs is challenging, as usually very low concentrations of the compound of interest need to be determined. Thus, an ultra-sensitive UHPLC–QqQ-MS/MS method was developed for simultaneous determination of HZ and CZ in biological fluid samples. The lower limit of quantification (LOQ) for HZ and CZ was calculated as 0.345 and 0.3696 ng/mL, respectively. Together with a reduced sample volume to 200 μL, it makes the developed method suitable for a sensitive multidrug forensic toxicological analysis. Samples were extracted with simple and fast liquid–liquid extraction (ethyl acetate, pH 9). The present method for the determination of HZ and CZ in human blood proved to be simple, fast, selective, and sensitive. The quantification by LC–MS/MS was successfully applied to the samples coming from 28 authentic biological fluids (blood, urine, vitreous humor, bile and stomach content), both antemortem and postmortem. The performed studies confirm that the developed method is characterized by a high extraction efficiency. Its accuracy, reproducibility, simplicity, and selectivity suggest its application in clinical, toxicological, and forensic laboratories. [ABSTRACT FROM AUTHOR]

Piperazines are a class of new psychoactive substances with hallucinogenic effects that affect the central nervous system by affecting the level of monoamine neurotransmitters. Abuse of piperazines will produce stimulating and hallucinogenic effects, accompanied by headache, dizziness, anxiety, insomnia, vomiting, chest pain, tachycardia, hypertension and other adverse reactions, and may even cause cardiovascular diseases and multiple organ failure and lead to death, seriously affecting human physical and mental health and public safety. The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community. The study of its pharmacological toxicology and analytical methods has become a research hotspot in the field of forensic medicine. This paper reviews the in vivo processes, sample treatment and analytical methods of existing piperazines, in order to provide reference for forensic identification.

Mass spectrometry (MS) is a widely used analytical technique including medical diagnostics, forensic toxicology, food and water analysis. The gold standard for quantifying compounds involves using stable isotope-labeled internal standards (SIL-IS). However, when these standards are not commercially available, are prohibitively expensive, or are extremely difficult to synthesize, alternative external quantification techniques are employed. We hereby present a novel, convenient and cheap quantification approach—quantification via post column infusion (PCI). As a proof of concept, we demonstrated PCI quantification for the immunosuppressant tacrolimus in whole blood using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The validation results met the criteria according to the guideline on bioanalytical method validation of the European Medicine Agency (EMA), achieving imprecisions and inaccuracies with coefficient of variation and relative bias below 15%. Anonymized and leftover whole blood samples from immunosuppressed patients receiving tacrolimus were used for method comparison (PCI quantification vs. conventional internal standard (IS) quantification). Both methods showed strong agreement with a Pearson correlation coefficient of r = 0.9532. This novel PCI quantification technique (using the target analyte itself) expands the quantification options available in MS, providing reliable results, particularly when internal standards are unavailable or unaffordable. With the current paper, we aim to demonstrate that our innovative PCI technique has great potential to overcome practical issues in quantification and to provide guidance on how to incorporate PCI in existing or new LC-MS methods. Moreover, this study demonstrated a more convenient method for correcting matrix effects in comparison to alternative PCI techniques. [ABSTRACT FROM AUTHOR]

Background and aim: Bromazolam, a novel designer benzodiazepine (NBD), exhibits potent sedative, hypnotic and anxiolytic effects, raising concerns regarding its potential for misuse and fatal outcomes, particularly when combined with opioids such as fentanyl. Despite limited documented fatalities globally, its use poses a significant threat, exacerbated by under‐reporting and a lack of routine testing. This study analysed NBD‐related deaths in a major US city over a 4‐year period. Methods: Analysis of accidental overdose deaths involving NBDs in San Francisco, CA, USA from 2020 to 2023, was performed utilizing medico‐legal death investigations including comprehensive forensic toxicology, pathology and demographic information. San Francisco conducts thorough investigations into all non‐natural and sudden unexpected deaths, including routine alcohol and drug testing of decedents under its jurisdiction, including etizolam, flualprazolam, flubromazolam and bromazolam analysis. Results: There was a sudden surge in bromazolam‐related deaths, with 44 fatalities documented in 2023, contrasting with relatively fewer deaths related to other NBDs. Bromazolam fatalities frequently involved co‐ingestion with opioids, primarily fentanyl, and stimulants such as methamphetamine and cocaine. Demographic characteristics indicated a predominance of males, with a significant proportion lacking fixed addresses. Blood concentrations of bromazolam increased during the study period, suggesting heightened availability and/or purity in the community. Conclusion: There was a surge in bromazolam‐related deaths during 2023 in San Francisco, CA, USA, contrasting with relatively stable numbers of deaths associated with other NBDs over the preceding years. The findings underscore the urgency for enhanced death investigation, testing and reporting to facilitate targeted harm reduction strategies for individuals at risk of bromazolam‐related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Currently, there is a significant demand in forensic toxicology for biomarkers of cannabis exposure that, unlike ∆9-tetrahydrocannabinol, can reliably indicate time and frequency of use, be sampled with relative ease, and correlate with impairment. Oral fluid (OF) and exhaled breath condensate (EBC) are alternative, non-invasive sample matrices that hold promise for identifying cannabis exposure biomarkers. OF, produced by salivary glands, is increasingly utilized in drug screening due to its non-invasive collection and is being explored as an alternative matrix for cannabinoid analysis. EBC is an aqueous specimen consisting of condensed water vapor containing water-soluble volatile and non-volatile components present in exhaled breath. Despite potential advantages, there are no reports on the use of EBC for cannabinoid detection. This study developed a supported liquid extraction approach and LC-QqQ-MS dMRM analytical method for quantification of 25 major and minor cannabinoids and metabolites in OF and EBC. The method was validated according to the ANSI/ASB 036 standard and other published guidelines. LOQ ranged from 0.5 to 6.0 ng/mL for all cannabinoids in both matrices. Recoveries for most analytes were 60–90%, with generally higher values for EBC compared to OF. Matrix effects were observed with some cannabinoids, with effects mitigated by use of matrix-matched calibration. Bias and precision were within ± 25%. Method applicability was demonstrated by analyzing ten authentic OF and EBC samples, with positive detections of multiple analytes in both matrices. The method will facilitate comprehensive analysis of cannabinoids in non-invasive sample matrices for the development of reliable cannabis exposure biomarkers. [ABSTRACT FROM AUTHOR]

Background. The subject of this article is the role of forensic toxicology in post-mortem examinations using immunofluorescence methods, its implications and its role in providing conclusive evidence for both criminal and civil proceedings. The aim of the study is to verify the correlation between the mode of death and the ingestion of exogenous substances and, if positive, to identify the category of substances ingested and assess their role in the cause of death. Materials and methods. A laboratory study was carried out, consisting of several phases: pre-analytical phase; analytical phase; post-analytical phase. The variables analyzed were sex, cause of death, age. Abused substances tested: amphetamines, methamphetamines, barbiturates, benzodiazepines, cocaine, methadone, opiates, tricyclic antidepressants, delta-9-tetrahydrocannabinol (cannabis), alcohol. Conclusions. Retrospective analysis was performed on a total sample of 55 cases. The most relevant data emerged: cocaine with an incidence of 7.3% (4 cases out of 55), amphetamines with 5.4% (3 cases in total). The results of the screening tests were then subjected to confirmatory tests. There is an association between the use of certain exogenous substances and an increased risk of certain causes of death, such as overdose, traffic accidents, cardiovascular deaths, etc. This paper has highlighted the possibility of using first level immunological tests, such as immunofluorescence, to provide preliminary answers to the judicial authority immediately after autopsy, and a quantitative deepening with further second level tests, such as gas chromatography, as a gold standard to determine the cause of death. [ABSTRACT FROM AUTHOR]

This cross-sectional study aimed to assess the association between drugs and alcohol intake and sexual abuse in adolescents, otherwise defined as Drug Facilitated Sexual Assault (DFSA). We considered the survivors who accessed care at the Centre "Soccorso Violenza Sessuale" (SVS – Sexual Violence Relief Centre) in Turin (Italy), between May 2003 and May 2022. We found that 973 patients aged 13–24 among which 228 were victims of DFSA. Epidemiological and anamnestic aspects of the episode of sexual violence were examined, with a specific focus on investigating the alcohol and/or drug intake as reported by the victim, along with the results of the toxicological analysis. the study further accounts for the variations caused by the COVID-19 pandemic on DFSA-related accesses. Our findings show that 23% of adolescents accessing care at SVS were subjected to DFSA. Six out ten adolescents knew their aggressor, at times a partner (10%) oran acquaintance (43%). In 12% of cases violence was perpetrated by a group of people (12%). Almost 90% of young victims described alcohol consumption, while 37% reported drug use at the time of the assault. Alcohol taken alone or in combination with other substances was the most detected drug in our sample throughout the period considered. Given the large use of psychoactive substances among adolescents, it is imperative to implement harm reduction strategies alongside educational activities aimed at fostering awareness about consent. Health personnel should be trained to manage the needs of victims of DFSA clinically and forensically. [ABSTRACT FROM AUTHOR]

The impact of contextual bias has been demonstrated repeatedly across forensic domains; however, research on this topic in forensic toxicology is very limited. In our previous study, experimental data from only one context version were compared with the actual forensic biasing casework. As a follow‐up, this controlled experiment with 159 forensic toxicology practitioners was conducted, to test whether knowledge of different contextual information influenced their forensic decision‐making. Participants in different context groups were tasked to identify testing strategies for carbon monoxide and opiate drugs. The results of chi‐squared tests for their selections and two context groups exhibited statistically significant differences (p < 0.05 or p < 0.01). These findings show contextual information can bias forensic toxicology decisions about testing strategies, despite it is a relatively objective domain in forensic science. [ABSTRACT FROM AUTHOR]

Electronic cigarette liquids (e-liquids) can contain a variety of chemicals to impart flavors, smells and pharmacological effects. Surveillance studies have identified hundreds of chemicals used in e-liquids that have known health and safety implications. Ethyl acetate has been identified as a common constituent of e-liquids. Ethyl acetate is rapidly hydrolyzed to ethanol in vivo. Animal studies have demonstrated that inhaling >2,000 mg/L ethyl acetate can lead to the accumulation of ethanol in the blood at concentrations >1,000 mg/L, or 0.10%. A "Heisenberg" e-liquid was submitted to the Laboratory for Forensic Toxicology Research for analysis after a random workplace drug test resulted in a breath test result of 0.019% for a safety-sensitive position employee. Analysis of this sample resulted in the detection of 1,488 ± 6 mg/L ethyl acetate. The evaluation of purchased "Heisenberg" e-liquids determined that these products contain ethyl acetate. The identification of ethyl acetate in e-liquids demonstrates poor regulatory oversight and enforcement that potentially has consequences for breath ethanol testing and interpretations. The accumulation of ethanol in the breath from the ingestion/inhalation of ethyl acetate from an e-liquid used prior to a breath test may contribute to the detection of ethanol. [ABSTRACT FROM AUTHOR]

Amphetamine (AMP) and methamphetamine (METH) use is increasing globally. Illegal AMP is generally a racemic mixture, whereas AMP-containing attention-deficit hyperactivity disorder drugs prescribed in Iceland consist of S-AMP. AMP is also a main metabolite of interest after METH intake. Distinguishing between legal and illegal AMP intake is vital in forensic toxicology. A chiral UPLC–MS-MS method was used to determine the enantiomeric profile of AMP and METH in circulation in Iceland by analysing blood samples from drivers suspected of driving under the influence of drugs (DUID) and seized drug samples from 2021 and 2022. All seized AMP samples (n  = 48) were racemic, whereas all but one seized METH sample (n  = 26) were enantiopure. Surprisingly, a large portion of the enantiopure METH samples was R-METH. DUID blood samples positive for AMP (n  = 564) had a median blood concentration of 180 ng/mL (range 20–2770 ng/mL) and a median enantiomeric fraction (EFR) of 0.54 (range 0–0.73), whereas samples positive for METH (n  = 236) had a median blood concentration of 185 ng/mL (range 20–2300 ng/mL) and a median EFR of 0.23 (range 0–1). The findings of this study show a significantly lower blood concentration in drivers with only S-AMP detected compared with when the R-isomer is also detected. No significant difference in blood concentration was detected between the sample groups containing S-METH, R-METH or both enantiomers. The occurrence of R-METH in both seized drug samples and DUID cases indicates a change in drug supply and a need for better scientific knowledge on R-METH abuse. [ABSTRACT FROM AUTHOR]

With wider availability of synthetic and semi-synthetic cannabinoids in the consumer space, there is a growing impact on public health and safety. Forensic toxicology laboratories should keep these compounds in mind as they attempt to remain effective in screening for potential sources of human performance impairment. Enzyme-linked immunosorbent assay (ELISA) is a commonly utilized tool in forensic toxicology, as its efficiency and sensitivity make it useful for rapid and easy screening for a large number of drugs. This screening technique has lower specificity, which allows for broad cross-reactivity among structurally similar compounds. In this study, the Cannabinoids Direct ELISA kit from Immunalysis was utilized to assess the cross-reactivities of 24 cannabinoids and metabolites in whole blood. The assay was calibrated with 5 ng/mL of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and the analytes of interest were evaluated at concentrations ranging from 5 to 500 ng/mL. Most parent compounds demonstrated cross-reactivity ≥20 ng/mL, with increasing alkyl side-chain length relative to Δ9-tetrahydrocannabinol resulting in decreased cross-reactivity. Of the 24 analytes, only the carboxylic acid metabolites, 11-nor-9-carboxy-Δ8-tetrahydrocannabinol, 11-nor-9(R)-carboxy-hexahydrocannabinol and 11-nor-9(S)-carboxy-hexahydrocannabinol, were cross-reactive at levels ≤10 ng/mL. Interestingly, 11-nor-9(R)-carboxy-hexahydrocannabinol demonstrated cross-reactivity at 5 ng/mL, where its stereoisomer 11-nor-9(S)-carboxy-hexahydrocannabinol, did not. As more information emerges about the prevalence of these analytes in blood specimens, it is important to understand and characterize their impact on current testing paradigms. [ABSTRACT FROM AUTHOR]