Abstract Duloxetine, a serotonin–norepinephrine reuptake inhibitor (SNRI), is widely prescribed for depression, anxiety, neuropathic pain, and other chronic pain conditions. Its pharmacokinetics show substantial interindividual variability due to sex, age, smoking, and CYP2D6 metabolism. Postmortem (PM) interpretation is further complicated by unknown blood-to-plasma distribution and significant postmortem redistribution. This study analyzed duloxetine concentrations in 2006–2026 Finnish forensic cases (N = 798), including fatal poisonings, polysubstance intoxications, and incidental findings. The median PM concentration of femoral venous blood samples was 0.16 mg/L, close to the upper therapeutic range of clinical plasma samples, while the mean concentration (0.33 mg/L) was twice as high. Based on our studies and data from the literature, toxic concentrations began at approximately 0.6 mg/L and fatal concentrations at 1–2 mg/L. In 13 fatal duloxetine poisonings, concentrations ranged from 0.46 to 9 mg/L, representing suicides and accidental over-dosing. In cases with both antemortem (AM) and PM samples, PM levels were on average 110% higher, indicating slight redistribution. Drug–drug interactions involving CYP2D6 inhibitors or substrates were present in several cases but did not fully explain the highest duloxetine concentrations. These findings highlight the need for cautious interpretation of PM duloxetine levels, especially in polysubstance intoxications and in individuals with impaired metabolism.
Abstract Novel psychoactive substance (NPS) benzodiazepines, such as bromazolam, present significant public health and safety risks due to their high potency, unpredictable effects, and frequent presence in forensic casework, often in combination with opioids. Their impact on driving impairment remains poorly understood, creating challenges for law enforcement and forensic toxicology. This study examines bromazolam associated driving investigated cases submitted to the Tennessee Bureau of Investigation (TBI), analyzing 289 forensic cases, with 41 cases providing comprehensive toxicology and law enforcement data, including 31 Standardized Field Sobriety Tests (SFSTs) and 5 Drug Recognition Expert (DRE) evaluations. For the cases included in this report, bromazolam was only detected once in isolation. All other samples included substances such as THC, methamphetamine, and/or fentanyl. The most common purpose for a traffic stop was failure to maintain lane position and motor vehicle crashes. SFST results documented multiple impairment related findings particularly during the walk-and-turn test; however, because most cases involved other potentially impairing substances, these findings cannot be attributed specifically to bromazolam. Limitations in forensic testing underscore the need for improved detection capabilities and law enforcement training. This study emphasizes the importance of monitoring and modification of forensic toxicology methodologies to effectively detect novel substances, while further research is needed to refine SFST and DRE protocols for more accurate impairment assessment and enhance road safety.
Abstract The emergence of highly potent synthetic opioids, including fentanyl analogues, nitazenes, and xylazine-associated drug mixtures, has created significant analytical challenges for forensic and toxicological laboratories. The aim of this study was to develop and validate a qualitative liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the screening of emerging synthetic opioids in oral fluid. Sample preparation was based on direct extraction of paper swabs with 500 μL of methanol containing 1% formic acid, followed by vortex mixing, ultrasonication, centrifugation, and direct LC–MS/MS analysis without evaporation or reconstitution. Method validation included selectivity and specificity, detection capability, matrix effects, inter-individual matrix variability, processed-sample stability, carryover, and intra-day precision. All target analytes fulfilled the established identification criteria at 1 ng/mL, the lowest concentration evaluated. Intra-day precision was acceptable, with RSD values ranging from 0.6% to 14.8%. Matrix effects were within 80–120% for the majority of analytes at both evaluated concentration levels, although compound-dependent ion suppression or enhancement was observed. Processed samples met the predefined stability criterion for 48 h at 4 °C and 72 h at − 20 °C, and carryover remained below the predefined acceptance criterion. Limited inter-individual variability was observed among the five donor matrices for the subset of analytes evaluated. The developed method provides a simple qualitative screening approach for an expanded panel of emerging synthetic opioids in oral fluid. Evaluation using authentic positive specimens is required to further establish its performance in forensic and DUID applications.
Abstract Malathion is one of the most widely used organophosphate insecticides worldwide. Although generally regarded as relatively safe, numerous accidental and intentional poisoning cases have been reported, including fatalities. However, interpretation of postmortem blood concentrations is challenging because reported concentrations vary widely among fatal cases, and malathion may be undetectable in postmortem blood despite documented exposure. Postmortem loss of intact malathion from blood may occur, and no definitive lethal concentration or diagnostic criteria for malathion poisoning have been established. We report the case of an elderly woman in her 80s who was found dead outdoors. Toxicological analysis revealed the presence of malathion, ethylbenzene, and xylenes in blood and cerebrospinal fluid (CSF), and the death was attributed to mixed intoxication. Malathion concentrations were 0.89 μg/mL in cardiac blood, 0.70 μg/mL in femoral blood, and 2.6 μg/mL in CSF, with higher levels in CSF than in blood. This difference may partly reflect the substantially lower protein content of CSF and its negligible red blood cell content, which may reduce protein-associated loss of free malathion. These findings suggest that CSF may be a useful complementary matrix for evaluating malathion in postmortem cases.
Abstract Toxicological analysis is an integral part of forensic death investigations. However, analysis is sometimes complicated by postmortem changes, and blood might not always be useable or available due to postmortem redistribution or degradation. In these cases, brain tissue can be useful as the brain is more protected against trauma, putrefaction, postmortem redistribution, skeletonization, and severe blood loss. However, reference concentrations of drugs in brain tissue are still scarce. This study aimed to report brain concentrations and brain–blood ratios for 122 compounds including drugs of abuse, pharmaceuticals, and metabolites frequently detected in forensic autopsy cases. In total, 2264 cases were collected over an 11-year period and retrospectively categorized as having either toxic or therapeutic levels of detected compounds based on blood concentrations. Toxic and therapeutic concentrations showed considerable overlap in both blood and brain due to drug tolerance and multi-drug combinations. Brain–blood ratios were highest for compounds with direct function on the central nervous system, especially antidepressants and sedative-hypnotics. The reported brain concentrations and brain–blood ratios can serve as reference values for interpretation of drug concentrations in brain tissue and the evaluation of cause of death in future forensic investigations.
