Gabapentinoids in Ireland 2010 to 2020: An observational study of trends in gabapentinoid prescribing, law enforcement drug seizures and postmortem toxicology.

AIMS: We explored trends in gabapentinoid prescribing, drug seizures and postmortem toxicology using a national pharmacy claims database, law enforcement drug seizures data and a population-based postmortem toxicology database. METHODS: Gabapentinoid prescribing rates per 100 000 eligible population (2010-2020), annual number of drug seizures involving gabapentinoids (2012-2020) and gabapentinoid detection (positive) rates per 100 postmortem toxicology case (2013-2020) were calculated. Negative binomial regression models were used to evaluate longitudinal trends for gabapentin and pregabalin separately. RESULTS: Gabapentin (adjusted rate ratio [RR] 1.06, 95% confidence interval [CI] 1.05-1.06, P < .001) and pregabalin (adjusted RR 1.08, 95% CI 1.08-1.09, P < .001) prescribing increased annually, with higher rates of pregabalin (vs. gabapentin) observed every year. Drug seizures involving pregabalin also increased over time (RR 1.54 95% CI 1.25-1.90, P < .0001). Of the 26 317 postmortem toxicology cases, 0.92% tested positive for gabapentin, and 6.37% for pregabalin. Detection rates increased for both gabapentin (RR 1.28, 95% CI 1.11-1.48, P < .001) and pregabalin (RR 1.13, 95% CI 1.11-1.48, P < .001) between 2013 and 2020. A total of 1901 cases (7.2%) tested positive for heroin/methadone; this sub-group had a higher detection rate for pregabalin (n = 528, 27.8%) and gabapentin (n = 41, 2.2%) over the study period, with a high burden of codetections for pregabalin with benzodiazepines (peaking at 37.3% in 2018), and pregabalin with prescription opioids (peaking at 28.9% in 2020). CONCLUSION: This study raises concerns regarding the wide availability of pregabalin in Ireland, including a growing illicit supply, and the potential for serious harm arising from poly drug use involving pregabalin among people who use heroin or methadone.

Alcohol and toxicological factors influencing fatal falls from height in the Greater Tokyo Area: a retrospective study.

Falls from height pose a significant public health concern in urban regions, including the highly urbanized Greater Tokyo Area. The Japanese population is characterized by high rates of suicide and psychoactive drug usage, underscoring the importance of investigating these attributes in falls from height. This study aimed to retrospectively analyze the alcohol and toxicological aspects influencing falls from height in the Greater Tokyo Area between 2014 and 2022 and compare the findings with existing reports on other populations. In total, 75 cases of falls from height and 159 cases of natural deaths were included. Consistent with previous findings, Fisher's exact test revealed a predominance of males (66.67%, 50/75) and young adults (57.33%, 43/75) in falls from height. Multivariate logistic regression analysis identified antidepressant usage as the most significant risk factor within the target population, while younger individuals under alcohol influence constituted another high-risk group. Notably, contradictory to other populations, female individuals involved in fatal falls in the Greater Tokyo Area exhibited a higher frequency of alcohol consumption than males (48.00%, 12/25 vs. 26.00%, 13/50), and most of them were associated with suicide (83.33%, 10/12). These findings elucidate the population characteristics that pose a high risk for fatal falls from height in Japan and can serve as a reference for other Asian populations residing in similar megacities.

Prevalence of alcohol-impaired driving: a systematic review with a gender-driven approach and meta-analysis of gender differences.

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.

Pro-active drug-facilitated crimes (DFC): a study in the Department of Forensic Medicine of Paris, France.

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.

Morphine concentrations in fatalities after palliative treatment of acute burn injury.

The evaluation of a morphine concentration in postmortem blood is routine for a forensic toxicologist. We here report three fatal cases where we found high morphine concentrations with 7.96, 4.30, and 5.82 mg/l in femoral blood that have to be estimated as unusually high. All these individuals died due to severe burn injuries and obtained morphine in the context of their palliative care in the last hours of their lives. According to the autopsy results, the cause of death in case 1 was burn disease with burns of about 90% of the body surface area (BSA), case 2 burn trauma, and case 3 burn shock. Besides morphine, propofol, fentanyl, sufentanil, midazolam, diazepam, lorazepam, cefazolin, and rocuronium were detected in femoral blood. The findings fitted well with the detailed clinical documentation. Further evidence of therapeutic concentrations of quetiapine, duloxetine, and melperone could be matched to preexisting medication of the individuals. Physiologically based pharmacokinetic modelling (PBPK) was applied, developed for the intravenous administration of morphine, to find an explanation for the high morphine concentrations in femoral blood. Quantification of morphine in body fluids and tissue was performed to calculate morphine tissue concentration ratios to the morphine concentration in femoral blood. The presented cases show that pharmacokinetic simulations can reflect decreased renal clearance and decreased hepatic metabolism in general. However, this prediction is not sufficient to explain the high morphine concentrations in femoral blood measured here. It can be assumed that burn shock in particular leads to altered pharmacokinetics, namely decreased distribution of morphine.

Intoxications involving methoxyacetylfentanyl and U-47700: a study of 3 polydrug fatalities.

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.

Chemical investigation of biological trace evidence; toxicological screening of waste residues obtained from DNA extraction processes.

In a forensic scenario, if biological stains are found in very small quantities, these are usually collected for DNA analyses, considered essential for the forensic investigation and thus excluding possible investigations by other forensic disciplines as forensic toxicology. We developed an experimental study to evaluate the feasibility of analyzing DNA extraction residues obtained from DNA extraction procedures to perform toxicological analysis, with the aim to extract both genetic and toxicological information without affecting or compromising the genetic sample and/or DNA extraction. DNA extraction from four blood samples (fortified with 5 molecules of interest with a final concentrations of 1 µg/mL, 100 ng/mL, 10 ng/mL and 5 ng/mL, respectively) were analyzed with QIAGEN QIAmp® DNA Mini kit. Three waste residues collected from the DNA extraction were analyzed for the toxicological investigation via Solid-Phase Extraction and High-Performance Liquid Chromatography-Tandem Mass Spectrometry analyses (Thermo Scientific™ TSQ Fortis™ II Triple-Quadrupole Mass Spectrometer). The analytical investigation revealed that our analytes of interest were detected in two different residues of the DNA extraction procedure, allowing both genetic and toxicological analyses without affecting the DNA identification. At last, the experimental protocol was applied to a hypothetical case, with encouraging results and allowing the identification of our molecules of interest.

Victims of drug facilitated sexual assault aged 13-24: a cross sectional study on the pool of users of a sexual violence relief centre in Northern Italy.

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.

Development of new matrix reference materials for quantitative urine analysis in drug tests.

Accurate quantitative analyses require standardized methods to control and improve the analytical process in the laboratory. The availability of urine reference materials (RMs) may offer a feasible option to improve the accuracy of urine analysis and to control matrix effects. This paper presents the complete process of the development of matrix RMs in urine, including sample preparation, homogeneity, and stability studies, as well as uncertainty assessment. A freeze-drying process was developed, and freeze-dried human and pig urine samples were prepared and verified to have comparable homogeneity to liquid samples and higher stability than liquid human, pig, and artificial urine samples at 4℃ or room temperature and under extreme conditions. A total of 21 authentic urine samples from August 2022 were measured with freeze-dried RMs and spiked urine samples, and the reliability of the quantification of the RMs was compared. The freeze-dried human urine matrix RM appeared to be an excellent tool for daily quality control, as it showed high stability and gave the most consistent results with spiked samples.

Quantification of 108 illicit drugs and metabolites in bile matrix by LC-MS/MS for the toxicological testing of sudden death cases.

Sudden death could occur after assumption of illicit drugs for recreational purposes in adults or after intoxication in children, and toxicological testing would help identify the cause of the death. Analytical methods sensitive and specific for the quantification of a great number of drugs and metabolites in at least 2 matrices should be used. Bile, collected postmortem, may be considered a specimen alternative to blood and urine to perform toxicological testing because of its extended detection window. The present study proposed a LC-MS/MS method to quantify 108 drugs and metabolites in bile. Compounds belonging to the drugs of abuse classes of amphetamines, benzodiazepines, cocaine derivatives, barbiturates, opioids, z-drugs, and psychedelics were analyzed. The sample preparation is simple and does not require solid-phase extraction. The proposed method showed an appropriate selectivity, specificity, accuracy, and precision of the calibrators and quality controls tested (precision < 15%; accuracy < 100 ± 15%). The sensitivity allowed to identify low amounts of drugs (e.g., morphine limit of detection = 0.2 µg/L; limit of quantification = 1.1 µg/L). There is no significant matrix effect, except for buprenorphine and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol. Carry-over was not present. Analytes were stable at least for 1 month at - 20 °C. Analyzing 13 postmortem specimens, methadone (50%), and cocaine (37.5%) resulted to be the most prevalent consumed substances; the concentrations quantified in bile resulted to be higher than the ones in blood suggesting bile as a potential new matrix for identifying illicit drugs and their metabolites.

In vitro structure-activity relationships and forensic case series of emerging 2-benzylbenzimidazole 'nitazene' opioids.

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 (ß-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.

Adulterants present in the San Diego county fentanyl supply: a laboratory analysis of seized law enforcement samples.

BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.

Application of UHPLC-QqQ-MS/MS Method for Quantification of Beta-Adrenergic Blocking Agents (ß-Blockers) in Human Postmortem Specimens.

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 ß-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.

A case of fatal poisoning caused by etomidate: evidence from pathological and toxicological analyses.

Etomidate is a nonbarbiturate sedative derived from imidazole. Prolonged and excessive use of etomidate can lead to the suppression of adrenocortical function, myoclonus, and even death. This report describes a rare case of a 47-year-old man who died from acute intoxication after oral ingestion of liquid containing etomidate. The cause of death was conclusively attributed to etomidate based on a comprehensive investigation, including autopsy, histopathological examination, toxicological analysis, and biochemical analysis. This is the first reported case of a fatality solely resulting from the oral ingestion of etomidate, which can provide valuable insights for future forensic investigations involving etomidate poisoning. Therefore, it is imperative to share this case with the scientific community.

Unusual concentration of tramadol detected in cadaver in the last stage of decomposition and in fly larvae in the immediate vicinity: case report and literature review.

Determination of the manner and cause of death from skeletal remains is almost always very difficult and can be a challenge for medical examiners. At the end also on skeletal remains, it is possible to assess mechanical, chemical, and thermal injuries, although it can be usually impossible. Possibilities to analyze biological material for the presence of drugs are also limited. The present study describes a case of a homeless man's skeletal remains on which a large number of fly larvae were found. Unusually high concentration of tramadol (TML) in the bone marrow (BM) = 4530 ng/g, muscle (M) = 4020 ng/g, and fly larvae (FL) = 280 ng/g was detected using a validated GC/MS method. In all analyzed samples, caffeine and N-desmethyltramadol (except BM) were qualitatively determined. Autopsy findings and toxicological analyses of the BM suggested that the cause of death could probably be intoxication by TML. It is apparent from the reviewed literature that analysis of TML in the late stages of decomposition of human body is rarely performed. Literature is predominantly focused on animal studies. Thus, TML concentrations analyzed in BM, M, or FL could be found helpful in relation to evaluation of intoxication by this substance. However, the significance of the results obtained in the presented study should be confirmed by further analyses of BM, M, or FL, where TML would be proved in lethal concentration in the blood.

A serial analysis of hydrogen sulfide poisoning: three group accidents.

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.

Incidental detection of aluminum phosphide in abdominal subcutaneous fat- a rare reporting of chemical analysis findings in poisoning cases.

Aluminum phosphide (AlP) poses a significant health challenge in developing countries, primarily because of its accessibility to the unregulated market and the absence of specific antidotes. Although chemical analysis of routine viscera can provide valuable information regarding the type of poison present in the body during poisoning incidents, numerous factors can alter the test results of chemical analysis, such as decomposition changes, postmortem redistribution, and the chemical nature of drugs. Analytical methods are frequently impeded by the interference caused by coextracted putrefactive compounds, which can mask or alter the detection of drugs. This series of three cases is particularly noteworthy because it involves the postmortem detection of AlP in the abdominal subcutaneous fat of the deceased, a previously unreported occurrence. In the first case, the body showed findings of late postmortem changes, with stomach mucosa being congested and hemorrhagic, along with routine viscera, and abdominal subcutaneous fat was sent for toxicological analysis. To confirm these findings, in two further cases of suspected AlP poisoning, subcutaneous fat was sent along with routine viscera. Stomach mucosa in the other two cases showed findings similar to those in the first. In the third case, black paste-like material was noted as stomach content. All the cases revealed the presence of AlP in routine viscera samples and abdominal subcutaneous fat on gas chromatography-mass spectrometry (GC‒MS) analysis. Therefore, abdominal fat can serve as a suitable sample for toxicological analysis to identify the presence of AlP, even in cases with advanced putrefactive changes.

A retrospective review of methylamphetamine detected in child deaths reported to the Victorian Coroner, Australia.

This study investigated methylamphetamine (MA) exposures in the deaths of children (≤ 12 years old) reported to the Coroner in the state of Victoria, Australia, between 2011 and 2020. Demographics, autopsy findings including the cause of death, self-reported prenatal or caregiver drug use, child protection services information, and toxicological findings were summarized by descriptive statistics. Validated methods of liquid chromatography-tandem mass spectrometry were used in the analysis of drugs. There were 50 child deaths with MA detected in blood, urine, and/or hair with 64% (n = 32) identified in 2018-2020. Most children were 1-365 days old (66%, n = 33) and the cause of death was unascertained in 62% (n = 31) of cases. MA was toxicologically confirmed in hair (94%, n = 47) significantly more than blood (18%, n = 9). Prenatal or caregiver drug use was self-reported in 44% (n = 22) and 42% (n = 21) of cases, respectively. Moreover, only 54% (n = 27) of deceased children were a child protection client at their time of death. These findings suggest the number of deceased children exposed to MA has increased over the past 10 years, which is consistent with the greater supply of crystal MA in the Australian community. Hair analysis provided additional means to identify cases that were unknown to child protection services and may have implications for other children in the same drug exposure environment.

The analysis of ramipril/ramiprilat concentration in human serum with liquid chromatography-tandem mass spectrometry - interpretation of high concentrations for the purposes of forensic toxicology.

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.

Death following cylindrical battery ingestion associated with toxic manganese levels.

Cases of battery ingestion are well documented in the scientific literature, especially concerning button cell battery ingestion in children. In this instance, the authors present an atypical case of a young man who voluntarily ingested a cylindrical alkaline battery containing manganese. The patient died approximately a week later, despite not exhibiting any specific symptoms. The battery was found in the cecum during the autopsy, showing deterioration at its positive pole. The cecal mucosa exhibited two ulcerations without perforation. Histological analysis revealed intestinal ischemia in the cecum, with no microscopic lesions in other organs. Toxicology reports indicated high levels of manganese in both cardiac and peripheral blood. Considering all the results from the additional analyses, the experts concluded that the death was likely of multifactorial origin, associated with a toxic blood concentration of manganese. To the best of our knowledge, this is the first recorded death following the ingestion of a cylindrical battery, and the first instance of manganese intoxication resulting from the ingestion of an alkaline battery. The authors will present the case and provide a literature review to assess the extent to which the presence of manganese may have contributed to the fatality.