Drug concentrations in post‐mortem femoral blood compared with therapeutic concentrations in plasma

Flubromazolam is a potent triazole benzodiazepine with moderately long-lasting central nervous system–depressant effects relative to other benzodiazepines such as commonly prescribed diazepam. Flubromazolam has been studied in the living. However, there are no published reports including measured drug concentrations in post-mortem cases. We report five cases in which flubromazolam was detected in a systematic screen using high-resolution mass spectrometry and then quantified in femoral blood. In none of the five cases was the cause of death directly attributed to flubromazolam toxicity, as there was a variety of both sedative and stimulant drugs also present. However, it is important that the drug concentrations that were measured are made available for future post-mortem forensic interpretation.

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Post-Mortem Antipsychotic Drug Concentrations and Unexplained Deaths

The British Journal of Psychiatry ◽

10.1192/bjp.165.6.787 ◽

1994 ◽

Vol 165 (6) ◽

pp. 787-791 ◽

Cited By ~ 52

Author(s):

Nedzara Jusic ◽

Malcolm Lader

Keyword(s):

Drug Treatment ◽

Antipsychotic Drug ◽

Drug Regimen ◽

The Body ◽

Electrolyte Balance ◽

Post Mortem ◽

Unexpected Death ◽

Legal Cases ◽

Drug Concentrations ◽

Antipsychotic Drug Treatment

BackgroundThe relationship between antipsychotic drug treatment and sudden unexplained death remains unclear. The estimation of post-mortem blood drug concentrations should be helpful.MethodEight medico-legal cases were reviewed with respect to behaviour of patient, type and dosage of drug treatment, mode of death, post-mortem findings and drug concentrations.ResultsThe problems of evaluating such drug levels are discussed. Five of the eight patients had probably toxic concentrations of antipsychotic and/or antidepressants, which caused death, usually involving cardiac arrhythmias.ConclusionsIn cases of sudden unexpected death, a sample of blood from a peripheral vein should be obtained immediately death is pronounced or the body discovered, and sent for analysis. To minimise such fatalities, the patient should be monitored carefully, with ECG if feasible, and electrolyte balance checked. The drug regimen used should be kept simple and large doses of antipsychotics and/or antidepressants avoided wherever possible.

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Interpretation of melperone intoxication: post-mortem concentration distribution and interpretation of intoxication data

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2020-0181 ◽

2021 ◽

Vol 36 (3) ◽

pp. 233-237

Author(s):

Marek Dziadosz ◽

Katarina Bolte ◽

Wolfgang Rosenberger ◽

Michael Klintschar ◽

Jörg Teske

Keyword(s):

Concentration Distribution ◽

Method Development ◽

Standard Addition ◽

Lethal Concentration ◽

Post Mortem ◽

Tissue Samples ◽

Expert Opinions ◽

Lack Of Information ◽

Reference Concentration ◽

Femoral Blood

Abstract Objectives Since melperone abuse with lethal intoxication is common, expert opinions based on therapeutical and lethal concentration ranges can be considered as important. Because there is a lack of information about fatalities caused by melperone mono-intoxications and data on tissue samples with concentration distribution, the aim of this work is the examination of lethal concentration ranges of melperone and drug quantification in different matrices. Methods An LC-MS/MS method was applied for analyses performed in blood and tissue samples. Quantification based on standard addition and sample preparation on liquid–liquid extraction with 1-chlorobutane. An appropriate tissue homogenization was performed ahead of extraction with an IKA Ultra-Turrax-Tube-Drive®. A Luna 5 µm C18 (2) 100 Å, 150 × 2 mm analytical column was used for chromatographic separation and the elution was performed with two mobile phases consisted of A (H2O/methanol = 95/5, v/v) and B (H2O/methanol = 3/97, v/v) both with 10 mM ammonium acetate and 0.1% acetic acid. Results A multi-drug LC-MS/MS analytical method developed was applied successfully for melperone quantification in different post-mortem matrices. No analytical problems could be identified during method development and analyses of real samples. The melperone lethal concentration calculated in femoral blood of the drug mono-intoxication investigated was 10 mg/L. Melperone concentration distribution was presented for the first time. Conclusions The lethal reference concentration of melperone in femoral blood of 17.1 mg/L pointed out in different reference lists should be used with caution. Instead, a lower lethal melperone concentration should be considered. The post-mortem concentration distribution of the drug presented could be helpful in the interpretation of cases where no blood samples are available.

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Dental Plaque Concentrations of Methadone, Morphine and Their Metabolites in Opioid Replacement Therapy and in Post-Mortem Cases

Journal of Analytical Toxicology ◽

10.1093/jat/bkab081 ◽

2021 ◽

Author(s):

Kerstin Henkel ◽

Miriam Klima ◽

Volker Auwärter ◽

Markus J Altenburger ◽

Merja A Neukamm

Keyword(s):

Oral Cavity ◽

Replacement Therapy ◽

Dental Plaque ◽

Oral Intake ◽

Study Groups ◽

Post Mortem ◽

Dental Biofilm ◽

Intravenous Application ◽

Drug Concentrations ◽

Opioid Replacement Therapy

Abstract Non-mineralized dental biofilm (plaque) has potential as novel alternative matrix in forensic toxicology to prove drug use. The incorporation of illicit and medicinal drugs in dental plaque could take place through direct contact after oral or nasal intake, which can lead to high drug levels in the oral cavity, or indirectly via the secretion of drug-containing saliva, e.g. after intravenous application. Therefore, plaque samples from patients in opioid replacement therapy (ORT) and post-mortem plaque samples were analyzed and the drug concentrations were compared. The study comprised 26 plaque samples from ORT patients with different daily doses which were analyzed for methadone, morphine and their respective metabolites. Plaque samples were taken directly before the oral administration of the regular daily dose. Seventeen post-mortem plaque samples were analyzed, either from cases of lethal drug intoxications or after pain therapy with morphine. Plaque analysis was performed using LC-MS/MS after liquid extraction with acetonitrile. Plaque concentrations in ORT for methadone and its metabolite EDDP ranged from 42 to approx. 49,000 pg/mg (median 1,300 pg/mg) and from below 10 to 610 pg/mg (median 31 pg/mg), respectively. Morphine plaque concentrations in ORT ranged from 120 to 480 pg/mg (median 400 pg/mg). In lethal intoxication cases plaque concentrations were generally at least one order of magnitude higher than in the study groups with therapeutic substance use. This data will help to interpret drug findings in plaque. Additionally, the EDDP/methadone concentration ratio in plaque was lower after oral intake with contamination of the oral cavity (e.g. syrup) compared to cases with suspected intravenous application of methadone and could therefore indicate the drug administration route.

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Femoral blood concentrations of the designer benzodiazepine etizolam in post-mortem cases

Medicine Science and the Law ◽

10.1177/0025802420973814 ◽

2020 ◽

pp. 002580242097381

Author(s):

Laura J Hikin ◽

Paul R Smith ◽

Peter D Maskell ◽

Hassan Kurimbokus ◽

Emily Ashong ◽

...

Keyword(s):

Drug Abusers ◽

Post Mortem ◽

Limited Data ◽

Spectrometry Method ◽

Blood Concentrations ◽

Blunt Force Trauma ◽

The World ◽

Femoral Blood ◽

The Mean ◽

Multiple Drugs

Etizolam is a thienodiazepine that although licensed for clinical usage in Japan, India and South Korea is commonly abused and detected in post-mortem cases around the world. To date, there are limited data in the literature to allow for the interpretation of blood concentrations of etizolam in post-mortem cases. A liquid chromatography with tandem mass spectrometry method was used to quantitate etizolam concentrations in 28 post-mortem cases where etizolam was detected. The median concentration of etizolam in femoral blood was 8.5 ng/mL (range 1.0–172.0 ng/mL; n = 24); in antemortem plasma, the etizolam concentration range was 4–44 ng/mL ( n = 4). The mean age of the individuals abusing etizolam was 38.5 ± 8.4 years (median 39 years), with the majority being male (86%). In all of the cases, multiple drugs were detected, with the most common being pregabalin (61%) followed by morphine/heroin (54%), diazepam (54%) and benzoylecgonine (21%), illustrating the increasing problem of poly-substance use in drug abusers. The cause of death in the cases in which etizolam was detected was multi-drug toxicity in 87.5% of the cases, with 12.5% unrelated to drug use (hangings and blunt-force trauma). These data will further help forensic practitioners with the interpretation of post-mortem etizolam concentrations.

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Postmortem Drug Redistribution: A Compilation of Postmortem/Antemortem Drug Concentration Ratios

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa107 ◽

2020 ◽

Author(s):

Dylan Mantinieks ◽

Dimitri Gerostamoulos ◽

Linda Glowacki ◽

Matthew Di Rago ◽

Jennifer Schumann ◽

...

Keyword(s):

Drug Concentration ◽

Forensic Toxicology ◽

Mixed Effects ◽

Cardiovascular Drugs ◽

Drug Concentrations ◽

Femoral Blood ◽

Drug Dependent ◽

Drugs And Metabolites ◽

Concentration Ratios

Abstract Postmortem drug redistribution (PMR) is a well-known phenomenon in forensic toxicology with implications for medico-legal death investigations. Paired antemortem (AM) specimen and postmortem (PM) mortuary admission femoral blood drug concentrations from 811 coronial cases were used to construct a retrospective compilation of PM/AM drug concentration ratios for 42 parent drugs and metabolites. The median PM/AM ratios for all antidepressants were > 1 and consistent with PMR In contrast, the median PM/AM ratios of most benzodiazepines were < 1. The antipsychotics were varied (0.63–3.3) and suggest the mixed effects of PMR and drug instability. Amphetamines exhibited no trends (0.90–0.95) and are likely confounded by many factors. The PM/AM ratios of cardiovascular drugs, opioids and other drugs are also reported. This research represents an expansive retrospective compilation of paired AM and PM drug concentrations for many toxicologically relevant drugs. While the median PM/AM ratios demonstrate some drug-dependent trends, there was no obvious relationship between AM specimens and PM femoral blood taken at mortuary admission.

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Drug concentrations in post‐mortem specimens

Drug Testing and Analysis ◽

10.1002/dta.2662 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1338-1357 ◽

Cited By ~ 5

Author(s):

Raimo A. Ketola ◽

Pirkko Kriikku

Keyword(s):

Post Mortem ◽

Drug Concentrations

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Predictive equation to estimate post-mortem interval using spectrophotometric blood-colour values

Medicine Science and the Law ◽

10.1177/0025802418819611 ◽

2019 ◽

Vol 59 (1) ◽

pp. 36-41

Author(s):

Yosuke Usumoto ◽

Keiko Kudo ◽

Akiko Tsuji ◽

Yoko Ihama ◽

Noriaki Ikeda

Keyword(s):

Right Ventricular ◽

Left Ventricular ◽

Predictive Equation ◽

Mean Square ◽

Post Mortem ◽

Predictive Equations ◽

Post Mortem Interval ◽

Lower Root ◽

Femoral Blood ◽

Left And Right

Forensic pathologists use post-mortem phenomena to estimate the post-mortem interval (PMI). We have reported on the usefulness of post-mortem lividity spectrophotometric values to estimate PMIs. Here, we focused on blood colour, looking for associations between blood colour, age and PMI. We generated predictive equations for blood-colour values and the PMI. We included data from a total of 129 cadavers (84 males and 45 females). We measured the colour of 124 left ventricular blood ( L*l, a*l, b*l), 123 right ventricular blood ( L*r, a*r, b*r) and 57 femoral blood ( L*f, a*f, b*f) samples. We found no significant associations between blood colour and age or between blood colour and the PMI, but the values of a*l, b*l, a*r and b*r were significantly increased with increased age, and those of L*f, a*f and b*f were significantly decreased with increased PMI. We created equations to estimate blood colour. The equations for femoral blood colour had higher adjusted R2 values and lower root mean square error values than those for left and right ventricular blood colours. We generated equations to estimate PMIs using blood-colour values and autopsy findings. Our estimated PMIs up to 67 hours had accuracies within 8.84 hours, without measuring post-mortem lividity colour or considering the age of the deceased. This is the first study to estimate PMIs based on blood-colour spectrophotometric values.

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