Carbon monoxide (CO) is a gas that is readily absorbed by the lungs when inhaled. Once in the blood, it forms a complex with hemoglobin (Hb) in red blood cells known as carboxyhemoglobin (COHb), reducing the oxygen-carrying capacity of Hb and therefore disrupting the transport and delivery of oxygen throughout the body. The resulting lack of oxygen can be harmful and even lethal, making it important to be able to detect COHb in postmortem samples of relevant cases for determining a cause of death. Blood and spleen are the preferred specimens for the detection of CO because they are Hb rich, but these specimens may not always be available for collection during autopsy. This study aims to determine if liver tissue can be a reliable source for the detection and/or quantification of CO in postmortem specimens in the absence of blood or spleen. Liver homogenates and blood specimens from 25 postmortem cases with a positive CO result in blood (%COHb ≥10%) and 10 postmortem cases testing negative for CO in blood (%COHb <10%) were analyzed for COHb via headspace gas chromatography/ mass spectrometry (HS-GC-MS) and compared. Cases for which the blood produced a positive result for CO did not always result in a positive finding in the liver (%COHb ≥10%), even in cases with high levels of %COHb saturation (>50%). However, all cases that had a liver result ≥10% COHb had a corresponding blood result ≥10% COHb. If blood or spleen is not available for CO testing, liver may be tested as a potential indicator of CO exposure. A positive %COHb finding in the liver correlates with a positive %COHb result in blood, but negative results in liver are inconclusive and cannot rule out CO exposure.
Fentanyl prevalence has increased exponentially in all forensic toxicology case types since the start of the current epidemic in 2016. Prior to 2016, fentanyl detected in postmortem cases was typically seen from use or misuse of medicinal administration. However, with the current epidemic, fentanyl use is from the illicit drug market and concentrations are substantially higher complicating interpretation. Additionally, factors contributing to postmortem redistribution of fentanyl can play a large role in interpretation. In combination with peripheral blood (PPH), brain concentrations can aid interpretation due to the isolated and protected location of the brain. A total of 566 cases were evaluated, and after excluding four outliers, the 562 cases had an overall fentanyl PPH mean of 18 ng/mL, median of 10 ng/mL, and range of 0.53-555 ng/mL. Overall mean, median, and range of fentanyl concentrations in brain samples were 61, 34, and 0.73-3100, respectively. Three concentration ranges, low (≤10 ng/mL), medium (>10-50 ng/mL), and high (>50 ng/mL), derived from PPH were established to evaluate cases based on various concentrations. The median blood-to-brain ratio doubled between the low and high bins. There was a greater percentage of females in the high concentration bin than that in the low and medium bins. The younger age group, aged 15 to 24 years, showed a higher prevalence of fentanyl in the medium group than in the others. The blood: brain ratio for all cases had a mean of 0.36, a median of 0.29, and a range of 0.03-2.57. The wide range of blood: brain ratios indicated that using singular information to interpret the case can be misleading. However, it does show the benefits of testing brain samples in suspected overdose cases where the fentanyl blood concentrations are low.
Driving under the influence of cannabis is a significant public safety issue. Tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, can impair driving ability and when used in combination with alcohol, the level of impairment can increase. Case studies documenting blood concentrations of THC and associated observations of impairment in individuals suspected of impaired driving continue to provide important contributions to the scientific literature. Retrospective analysis was performed using data from impaired driving investigations in which THC alone, and in combination with alcohol, were the only findings in blood samples submitted to the Centre of Forensic Sciences between 2021 and 2023, inclusive. In cases where only THC was present, blood concentrations ranged from 1.1 to 72 ng/mL (mean 12 ng/mL, median 9.5 ng/mL). When both THC and alcohol were present, the mean blood THC concentration was 13 ng/mL, and the mean blood alcohol concentration was 145 mg/100 mL. The most common driving and Drug Recognition Expert (DRE) observations included collisions, erratic driving, eyelid tremors, poor balance and coordination, and bloodshot eyes. Observations of driving impairment were more frequently observed in cases where both THC and alcohol were detected in the blood. These findings provide additional data to inform the interpretation of blood THC concentrations in the context of DRE observations and suspected impaired driving investigations.
First-generation H1 antihistamines have central nervous system penetration and anticholinergic activity, with potential side effects including sedation, cognitive impairment, and anterograde amnesia. First-generation antihistamines pose risks in driving under the influence of drugs (DUID) and drug-facilitated crimes (DFC) forensic casework. A liquid chromatography-tandem mass spectrometry method was developed and validated for five first-generation H1 antihistamines: chlorpheniramine, diphenhydramine, doxylamine, hydroxyzine, and promethazine. The calibration range was 1-200 ng/mL with a 1/x linear calibration model for quantitative compounds, and the limit of detection was determined to be 0.5 ng/mL for all compounds. Bias and precision were acceptable, with minor but acceptable suppression observed at low and high concentrations. No exogenous or endogenous interferences were observed. Carryover was not detected after a 400 ng/mL sample. Processed samples were determined to be stable 24 h after initial injection when stored in the refrigerated multi-sampler. Authentic forensic specimens from DUID and DFC investigations showed a wide range of concentrations for diphenhydramine. Selected case reports are presented to demonstrate the applicability of the method. The high percentage of polysubstance cases, range of concentrations, and delayed sample collection in DFC cases underscore the importance of a sensitive and reproducible method for these first-generation antihistamines, especially in human-performance casework.
Methamphetamine ("shabu") is an increasing medico-legal and public safety concern in Western Saudi Arabia, with early postmortem surveillance in Jeddah indicating a > 500% rise in methamphetamine-involved deaths between 2016 and 2018. However, whether this increase reflects a temporary fluctuation or the onset of a sustained, evolving mortality pattern requires longer follow-up periods. Therefore, we retrospectively characterized methamphetamine-related medico-legal deaths investigated in Jeddah, Saudi Arabia, from 2018 to 2022 (n = 90) using comprehensive postmortem toxicology and validated multimatrix liquid chromatography-tandem mass spectrometry quantification. Case counts increased from 10 (2018) to 27 (2022), a 2.7-fold rise, with 56.7% (51/90) occurring in 2021-2022, indicating an upward phase after 2020. The manner of death was documented as accidental (65.6%; 59/90), suicide (17.8%; 16/90), or homicide (16.7%; 15/90), with suicide and homicide together accounting for 34.4% (31/90) of cases. Blood methamphetamine and amphetamine concentrations displayed a broad overlap across the manner of death (p = 0.718 and p = 0.558, respectively), supporting that the manner of death cannot be inferred from single-threshold concentrations. Across study periods, the median blood methamphetamine levels remained comparable, with overlapping interquartile ranges (overall p > 0.05), indicating that the increase in cases after 2020 reflected higher case numbers rather than higher typical blood concentrations. Toxicology profiles showed methamphetamine-only (43.3%), polydrug intoxication (32.2%), and methamphetamine with non-contributory co-detections (24.4%), with graded but overlapping median blood methamphetamine concentrations. The multimatrix concordance was strongest for vitreous humor (ρ = 0.845; n = 69), gastric contents (ρ = 0.800; n = 28), and bile (ρ = 0.729; n = 23), supporting the interpretation when blood is limited or compromised. These findings confirm the sustained and increasing methamphetamine mortality burden in Jeddah and support continuous forensic monitoring, routine multimatrix toxicology, and integrated interpretation to inform prevention and control efforts in the future.
Synthetic cathinones are a chemically diverse class of novel stimulants that continue to emerge in the U.S. and globally. Trends in overall and specific synthetic cathinone availability in the U.S. (as indicated by seizures) remain poorly characterized. We analyzed annual counts of reports submitted from 2010-2024 to the U.S. Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS). We grouped reports into chemical subclasses of beta-keto methylenedioxyamphetamines ("-ylones"), pyrrolidinophenones ("pyrros"), and beta-keto amphetamines ("-drones"). Temporal trends in total reports and subclasses were modeled using negative binomial regression spline models. To further contextualize subclass trends, we descriptively examined the contribution of individual synthetic cathinones over time. Between 2010 and 2024, 178,892 synthetic cathinone reports were submitted to NFLIS, of which 73.3% were classified as -ylones, 19.9% as pyrros, 5.2% as -drones, and 1.6% as other. 68.7% of total reports were from the South, with 33.5% from Florida. Nationally, total reports increased sharply in 2010-2013, declined mid-period, rose again from 2019-2020, and then stabilized. Additional regional and temporal heterogeneity was noted across subclasses. We identified patterns of rapid emergence and replacement of individual compounds within subclasses, particularly within the -ylone subclass. Overall, we found substantial temporal, regional, and subclass-specific variation in synthetic cathinone reports to NFLIS from 2010-2024, largely driven by reports from the South and from successive cycles of replacement of -ylones. These findings emphasize the need to strengthen forensic and epidemiological surveillance of the evolving synthetic cathinone landscape in the U.S.
The growing emergence of new psychoactive substances (NPS) challenges traditional approaches to drug monitoring, highlighting a need for innovative surveillance strategies. We explored the potential to better understand the NPS market in Australia by combining wastewater analysis with toxicosurveillance programs. Focussing on a time of year of likely higher NPS and drug use, influent wastewater samples were collected from four Australian states (South Australia, Victoria, Queensland, and New South Wales) over the New Year period from 2019-2020 to 2024-2025. Clinical samples presenting between 15 December and 15 January each period from the toxicosurveillance systems Emerging Drugs Network of Australia (including Western Australia, South Australia, and Queensland), Emerging Drugs Network of Australia Victoria (Victoria) and Prescription, Recreational and Illicit Substance Evaluation-PRISE (New South Wales) were extracted. In total, 294 wastewater and 117 clinical samples were included in this work. A total of 46 individual NPS were found in both datasets. This included: 21 only in wastewater, 36 only in clinical, and 12 in both. Overall, 743 instances of NPS were found in all wastewater samples and 171 in clinical data. In wastewater samples, N, N-dimethylpentylone (54%), mitragynine (52%), and bromazolam (45%) were the most frequently detected. In the clinical samples, the most common were bromazolam (44%) and clonazolam (21%). Overall, synthetic cathinones and plant-based compounds were more prevalent in wastewater, and synthetic opioids and benzodiazepines in clinical samples. Differences in detected NPS classes illustrate the complementary nature of these surveillance systems. Higher wastewater concentrations may indicate broader use and lower acute harm than drugs identified clinically. Integrating these datasets with additional sources such as surveys, coronial records, police seizures, and drug-checking services can strengthen NPS monitoring.
Chronic stress has been associated with adverse health outcomes, including anxiety, depression, and cardiovascular disease. During pregnancy, stress-related biological changes may affect maternal and fetal health; however, assessing cumulative stress-related biomarkers remains challenging. Glucocorticoids (cortisol/cortisone) and endocannabinoids (lipid-based neurotransmitters) have been proposed as biomarkers related to stress physiology. Hair is a useful matrix for evaluating cumulative analyte exposure over extended periods because it is less affected by short-term fluctuations and circadian variation than blood, saliva, or urine. The aims of this study were to: (i) develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of glucocorticoids and endocannabinoids in hair, and (ii) apply the method to hair samples collected at delivery to describe glucocorticoid and endocannabinoid concentrations across pregnancy. The method consisted of 20 mg of pulverized hair incubated in 1 ml of methanol:acetonitrile (75:25) under ultrasound at 55°C for 2 h, and analyzed by LC-MS/MS. A total of 66 3-cm hair segments from 35 pregnant women across the three trimesters were analyzed. Glucocorticoids were detected in 62 segments (cortisol in 62 and cortisone in 54) and endocannabinoids in all of them (oleoylethanolamine and palmitoylethanolamine in all, 2-arachidonoylglycerol in 53, but none for arachidonoylethanolamide). In the 13 cases with segments from all three trimesters, no significant changes in endocannabinoids were observed, whereas glucocorticoids increased throughout pregnancy. These findings demonstrate that hair analysis enables reliable, longitudinal assessment of glucocorticoids and endocannabinoids during pregnancy, supporting its utility as a non-invasive monitoring tool.
Interpretation of postmortem toxicology results is complicated by postmortem redistribution (PMR), which can alter drug concentrations between tissues and blood (BL). This study evaluates brain (BR) to BL concentration ratios for amphetamine (AMP), methamphetamine (MAMP), cocaine (COC), benzoylecgonine (BE), cocaethylene (CE), and fentanyl (FENT) using postmortem casework data to evaluate the utility of BR tissue as an alternative matrix. BR:BL ratios varied widely across analytes: AMP (2.2-5.8), BE (0.2-2.1), CE (1.2-5.1), COC (0.1-5.8), MAMP (2.2-7.3), and FENT (1.1-24.8). Lipophilic compounds (AMP, CE, COC, MAMP, and FENT) generally exhibited ratios greater than one, consistent with preferential BR partitioning and susceptibility to PMR, whereas the polar metabolite BE showed ratios less than one, reflecting limited BR accumulation. FENT demonstrated the greatest variability, highlighting challenges in interpreting its postmortem concentrations. Correlations between BR and femoral BL concentrations were slightly positive for all analytes, indicating that BR concentrations may not be reliable proxies for BL levels. Evaluation of select antemortem cases and outliers revealed additional influences on BR:BL ratios, including survival time, drug stability, route of administration, and polysubstance use. COC instability and hydrolysis to BE, as well as incomplete drug distribution in rapid deaths, contributed to atypical ratios. Overall, BR:BL ratios are highly analyte dependent and influenced by both pharmacokinetic properties and postmortem factors. While BR tissue may provide useful complementary information when BL is unavailable, it should not be used as a direct substitute for BL in toxicological interpretation. These findings underscore the need for further research to expand BR:BL datasets across drug classes.
Drug-facilitated sexual assault (DFSA) refers to sexual acts where the victim is incapacitated by the effects of psychotropic substances, causing impaired ability to prevent an attack and/or provide informed consent. To date, the level of understanding of the prevalence of the specific drugs involved in DFSA has been limited. This review examines global toxicological case data to assess the prevalence of tramadol, a widely prescribed opioid analgesic, in the context of DFSA. Tramadol was confirmed in reports across Africa, Oceania, Europe, the Middle East, and North America, with detection rates ranging from 1% to 33%. In these cases, 17 voluntary and involuntary drug combinations were identified including alcohol, opioids, benzodiazepines, Z-drugs, cannabinoids, and stimulants. These substances pose significant risk for both pharmacodynamic and pharmacokinetic interaction with tramadol, potentially altering plasma metabolite levels, clearance times and also central nervous system depression, facilitating DFSA and influencing forensic detection and interpretation of tramadol and its metabolites. Overall, this review underscores the significance of tramadol in DFSA casework and highlights the importance of drug-drug interactions in order to improve forensic analysis in DFSA casework and aid in legal action leading to victim support and closure.
Treatment with antipsychotics such as chlorprothixene, clozapine, olanzapine, and quetiapine can be associated with cardiovascular and metabolic risks and poisoning, making them highly relevant in toxicological investigations. Since antipsychotics primarily act within the central nervous system, brain tissue serves as an alternative or complementary matrix to femoral blood in toxicological analysis. This study aimed to retrospectively evaluate brain concentrations and brain-blood ratios across toxic and non-toxic levels in 466 postmortem cases involving chlorprothixene, clozapine, olanzapine, and/or quetiapine. Median concentrations in brain tissue across all cases were 0.20 mg/kg for chlorprothixene, 4.2 mg/kg for clozapine, 0.42 mg/kg for olanzapine, and 0.34 mg/kg for quetiapine. Corresponding brain-blood ratios remained stable across the examined concentration range with median ratios of 3.1 for chlorprothixene, 2.9 for clozapine, 2.6 for olanzapine, and 3.0 for quetiapine. The provided brain concentrations and ratios can support further toxicological evaluations of postmortem cases.
We report a case of a previously healthy 3-year-old girl who developed acute altered consciousness, agitation, and visual hallucinations consistent with an anticholinergic toxidrome. Initial examinations were unremarkable, and urine immunoassay screening (SIGNIFY™ ER) was negative. Serum analysis by liquid chromatography-quadrupole time-of-flight mass spectrometry identified chlorpheniramine and scopolamine, while excluding other agents. Concentrations were 370 ng/mL for chlorpheniramine and 1 ng/mL for scopolamine, both near reported toxic ranges. An empty blister pack of 22 pediatric motion sickness tablets was found at the patient's home, confirming accidental overdose of an over-the-counter (OTC) anti-motion sickness medication. This case demonstrates the diagnostic utility of high-resolution mass spectrometry in pediatric poisoning, particularly for drugs not detected by routine screening. It represents a rare report documenting quantitative confirmation of both chlorpheniramine and scopolamine in a child, with correlation between serum concentrations and clinical presentation. Scopolamine is highly toxic even at low concentrations, and pediatric cases with measured blood levels are exceedingly rare. Our findings highlight the need to consider additive or synergistic toxicity in OTC formulations containing multiple anticholinergic agents and emphasize the importance of caregiver education regarding the potential risks of OTC medications often perceived as safe.
Drug-facilitating sexual assault (DFSA) corresponds to sexual activity occurring whereas the victim is unable to express consent due to the action of drugs. Although the use of sedative and amnesic drug in DFSA, such as benzodiazepines and gamma-hydroxybutyrate, is widely described in the medical literature, there is a lack of information regarding the involvement of amphetamine derivatives in this context, particularly synthetic cathinones. Herein, we report a case of a 19-year-old woman who presents herself to the emergency department following an acute alcoholic intoxication and a suspected DFSA after going to a nightclub. The emergency toxicological screening on the plasma and urine of the patient, performed through liquid chromatography coupled to high resolution tandem mass spectrometry in target and non-target mode and with gas chromatography coupled to high resolution mass spectrometry, enabled the detection of 4-bromomethcathinone, a new psychoactive substance (NPS) of the cathinone family. The demethylated and reduced metabolites of the drug were also found in both plasma and urine. No other substance was identified except ethanol, which was quantified in gas chromatography-flame ionization detection, and diazepam with its metabolites, this last one having been administrated in the emergency department. As far as we know, this report described the first case of DFSA involving this halogenated derivative of cathinone and consequently, highlights the need for toxicologists to systematically investigate with specific analytical methods the potential presence of NPS in cases of DFSA.
Bone marrow (BM) has emerged as a valuable alternative matrix in postmortem toxicology, when conventional samples such as blood or soft tissues are unavailable, degraded or contaminated. BM, due to its protecting anatomical site within the medullary cavity, slows down decomposition, limits environmental and microbial interference and enables the preservation of xenobiotics over extended postmortem intervals. This review summarizes the updated literature on BM anatomy, sampling site, xenobiotic distribution and stability, as well as the influence of postmortem redistribution (PMR) and putrefaction for toxicological interpretation of the analytical results. Evidence indicates that drug distribution in BM is governed by tissue vascularity and analyte physicochemical properties, with lipophilic compounds often reaching higher concentrations in BM than in blood. Numerous studies demonstrate the long-term stability of drugs such as amphetamines, benzodiazepines, sedative-hypnotics and ethanol in BM, even in severely decomposed, burned, or skeletonized remains. While BM shows reduced susceptibility to PMR and putrefaction compared to blood and soft tissues, post-collection stability depends on proper storage conditions. Findings from human forensic cases assess the detectability of a wide range of illicit and therapeutic substances in BM, supporting its utility in reconstructing ante-mortem drug exposure when traditional matrices are compromised. Despite promising results, data remain limited, and further research is needed to refine interpretative frameworks and establish standardized protocols for BM sampling, analysis, and toxicological evaluation.
Immunoassay-based urine drug screens are widely employed in clinical toxicology due to their speed, low cost, and ease of automation. However, these assays are inherently limited by antibody cross-reactivity, which can result in false-positive findings and incorrect interpretations with major implications for patient care, employment, and legal outcomes. This review updates prior literature by analyzing reported false-positive interferences published between 2013 and 2024 across commonly screened drug classes, including opioids, amphetamines, benzodiazepines, cannabinoids, barbiturates, phencyclidine (PCP), cocaine, ethanol, and ethyl glucuronide. A total of 61 studies met inclusion criteria from 569 unique publications retrieved via PubMed. Each report was categorized by level of evidence, ranging from single case reports to controlled spiking experiments. Despite advances in antibody specificity, immunoassay drug screens remain presumptive and require confirmation by orthogonal techniques such as gas or liquid chromatography coupled with mass spectrometry (GC-MS or LC-MS/MS). This review provides updated reference data on known interferents, emphasizes the need for laboratorian-clinician communication, and supports continued education on assay limitations. Reliable interpretation of presumptive immunoassay drug screen results remains essential to prevent inappropriate clinical care decisions.
The structural similarity of positional isomers of fentanyl analogs makes their forensic differentiation difficult, particularly when the parent compounds exhibit similar chromatographic behavior and product-ion spectra. This study evaluated the differentiation of 2-, 3-, and 4-fluorofuranylfentanyl (2-, 3-, and 4-FFF) using high-performance liquid chromatography-mass spectrometry (HPLC-MS) and human liver microsomes (HLMs). The synthesized positional isomers were analyzed using gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and HPLC-ion trap-time-of-flight mass spectrometry (HPLC-IT-TOF-MS). Although the parent isomers were separated by GC-MS, their retention times and product-ion spectra obtained by HPLC-MS/MS were highly similar under the present conditions. Incubation with HLMs supplemented with NADPH, UDPGA, and alamethicin produced three Phase I metabolic categories: an oxidative N-dealkylated metabolite of FFF (M1), monohydroxylated FFF metabolites (M2a and M2b), and an amide hydrolysis product of FFF (M3). Glucuronide conjugates were not detected under the present analytical conditions. Although M1 was the predominant metabolite, M1 did not retain the complete FFF structure. M2a and M2b were putatively assigned as monohydroxylated metabolites that retained the complete FFF structure, and may therefore support the differentiation of FFF positional isomers, although their retention times did not allow the differentiation. M3, which did not retain the complete FFF structure, showed distinct retention times among the three positional isomers, providing chromatographic information useful for metabolite-based differentiation. The in vitro elimination half-lives differed among 2-, 3-, and 4-FFF under the present HLM conditions, suggesting possible differences in the pharmacokinetic properties of these positional isomers. These findings indicate that HPLC-MS analysis using HLMs provides useful analytical information for differentiating FFF positional isomers.
This study describes the contextual factors and scientific data associated with fentanyl-related deaths among individuals aged 0-17 years in North Carolina. Using information from the North Carolina Medical Examiner System from 2015 to 2024, 138 pediatric fentanyl deaths were identified. Manually abstracted scene information, toxicology results, and pathological findings allowed for a rarely examined in-depth analysis of circumstances surrounding these deaths. Children less than 2 years (n = 33, 1.38 per 100 000) and adolescents aged 15-17 years (n = 80, 1.96 per 100 000) experienced a fentanyl-related death rate higher than the statewide pediatric fentanyl-related death rate of 0.60 per 100 000 residents. Among children less than 2 years, 78.8% of overdose onset occurred in the decedent's primary residence, and drugs or paraphernalia were present at the scene in 51.5% of cases. Co-sleeping was documented in 60.6% of deaths, with 80.0% occurring in adult beds. Postmortem blood concentrations of fentanyl among children less than two years ranged from less than 0.50 to 280 ng/mL (mean 27.0 ng/mL, median 17 ng/mL). Among adolescents, 62.5% of overdose onset occurred in the decedent's primary residence, followed by a friend's residence (13.8%). History of substance use was documented in 82.5% of cases and drugs or paraphernalia were present in 67.5% of cases. Blood concentrations of fentanyl among adolescents ranged from less than 1.0 to 330 ng/mL (mean 21.7 ng/mL, median 11.0 ng/mL). Scene investigation and documentation allow for the recognition of behavioral trends, which can be targeted for age-specific overdose prevention strategies. Among decedents less than 2 years, notable trends included children co-sleeping in adult beds with access to drugs and drug waste and/or prolonged periods without supervision. Among older adolescents, several cases involved suspected counterfeit pharmaceuticals and/or periods of non-contact with primary caregivers. Improved workflows for pediatric medicolegal death investigation and electronic reporting strategies are already underway.
Motor vehicle fatalities continue to be a leading cause of preventable death in the United States. Beginning in 2019, there was a steady uptick in traffic fatalities nationally, which peaked in 2021. The state of Connecticut has experienced similar trends with increases in traffic fatalities over the last several years. The focus of this review was to evaluate drug positivity in traffic-related fatalities that occurred in Connecticut between January 1, 2020 and December 31, 2024. Cases related to traffic fatalities were identified by the state's Office of the Chief Medical Examiner. Deaths of drivers, passengers, and pedestrians were used for the data set. A total of 1,816 fatal motor vehicle incidents were reviewed. Of these, 312 cases lacked toxicology results, and 5 cases had testing canceled; both were excluded from substance-related analyses. Among the remaining 1,499 cases with available toxicological data, 1,084 (72%) had at least one positive toxicology finding. Drug positivity was identified in 75% (710 of 948) of driver fatalities, 66% (125 of 188) of passenger fatalities, and 67% (221 of 327) of pedestrian fatalities. The most frequently encountered drugs across all three classes of decedents were ethanol, delta-9 tetrahydrocannabinol, and fentanyl. These findings underscore the pervasive role of drugs and alcohol across all categories of traffic-related deaths and highlight the ongoing need for preventive strategies, toxicology testing, and targeted public safety interventions.
Interpretation of postmortem (PM) γ-hydroxybutyric acid (GHB) remains challenging due to endogenous production and PM increases in concentration associated with decomposition. Existing interpretation guidelines primarily rely on a single criterion, such as concentration thresholds or urine-to-blood ratios. In San Francisco, routine and unbiased implementation of GHB testing across all casework generated a large dataset including 1865 GHB detections in PM blood or urine, of which 552 were paired peripheral blood and urine samples. Cases were categorized as acute exogenous use, confirmed exogenous use, or no indication of use based on toxicological and investigative findings. Peripheral blood concentrations in cases with no indication of use did not vary significantly by age, gender, race, or manner of death but were significantly higher in decomposed cases. While existing guidelines effectively identify endogenous levels, the proposed hybrid model, combining peripheral blood concentration (B) with urine-to-blood ratio (U/B), enables further classification into no exogenous use, possible exogenous use (B > 5 mg/L and U/B > -0.05 × B + 4), and acute exogenous use (B > 50 mg/L and U/B > -0.05 × B + 10). The model was evaluated and compared to existing guidelines. Internal applicability was assessed using recent casework, and external applicability was evaluated using an independent dataset from Québec, Canada. The hybrid model demonstrated improved performance, achieving substantially higher positive predictive value when compared to existing guidelines, while maintaining equal or improved performance measures across other metrics. This approach provides a conservative, evidence-based framework for distinguishing acute exogenous GHB use in PM casework.
