Site Dependence of Drug Concentrations in Postmortem Blood--A Case Study (original) (raw)
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Postmortem Brain–Blood Ratios of Codeine, Fentanyl, Oxycodone and Tramadol
Journal of Analytical Toxicology, 2020
The analgesics, codeine, fentanyl, oxycodone and tramadol, frequently occur in postmortem cases and determining their role in the cause of death can be challenging. However, postmortem blood is susceptible to redistribution and may not be available in cases of severe blood loss, putrefaction or burns. Brain tissue may serve as a viable supplement to blood or on its own, as it is resistant to postmortem redistribution and often available as a sample matrix when blood is not available. We present brain and blood concentrations and brain-blood ratios of the four analgesics from 210 autopsy cases. The cases were classified according to the presumed cause of death: A: The compound was believed to have solely caused a fatal intoxication. B: The compound was assumed to have contributed to a fatal outcome in combination with other drugs, alcohol or disease. C: The compound was not regarded as being related to the cause of death. Blood and brain samples were prepared by automatic solid phase extraction and quantified by liquid chromatographymass spectrometry. The squared correlation coefficients between concentrations in brain tissue and blood ranged 0.45-0.91. The median brain-blood ratios were codeine 1.8 (range 0.47-4.6), fentanyl 2.1 (range 0.29-16), oxycodone 1.8 (range 0.11-6.0) and tramadol 1.8 (range 0.047-6.8). A significantly higher brain-blood ratio of codeine was observed in cases where heroin had been administered, although there was a wide overlap. Intravenous and transdermal fentanyl administration could not be distinguished based on the blood or brain concentration or the brainblood ratio. The results of this study may benefit the toxicological investigation in postmortem cases where one of the four analgesics are suspected of having contributed to or caused a fatal intoxication.
Postmortem Distribution of Tramadol, Amitriptyline, and Their Metabolites in a Suicidal Overdose
Journal of Analytical Toxicology, 2005
A case report involving a 34-year-old white male who was found dead at home by his roommate is presented. At the time of his death, he was being treated with tramadol/acetaminophen, metaxalone, oxycodone, and amitriptyline. The decedent's mother stated that he had been taking increasing amounts of pain medication in order to sleep at night. There were no significant findings at autopsy; however, toxicology results supported a cause and manner of death resulting from suicidal mixed tramadol and amitriptyline toxicity. This case reports the tissue and fluid distribution of tramadol, amitriptyline, and their metabolites in an acutely fatal ingestion in an effort to document concentrations of these analytes in 12 matrices with respect to one another to assist toxicologists in difficult interpretations.
Toxicological identification of diphenhydramine (DPH) in suicide
Forensic Science, Medicine, and Pathology, June 2013, Volume 9, Issue 2, pp 145-153
Diphenhydramine (DPH), an H1-antihistamine, is identified during postmortem toxicological analyses on a relatively rare but still regular basis. This study examines suicidal intoxications with DPH by analyzing blood and gastric content concentration levels. Twenty cases of DPH intoxications within a 10-year period (2000–2010) were discovered by screening the autopsy records of the Institute of Legal Medicine and Forensic Sciences (ILMFS) in Berlin, Germany. In four cases, DPH levels were lower than 1 μg/mL and hence were not considered likely to be responsible for causing death. In 11 cases, DPH played a role in the fatal episode, and five of these cases were monointoxications. Considering that more than 8,000 autopsies were performed by the ILMFS within the time period under examination, there is only one monointoxication case every 2 years, which makes it a rare occurrence. In two of these intoxications, DPH was only measured in toxic but not “lethal” concentrations in blood, with a concentration of 5 μg/mL being generally used as the cut off between categories according to forensic literature. This raises the question as to whether a strict boundary for a “lethal” blood concentration, as suggested in some literature, can be set and applied in any of these cases. This study shows that an individual interpretation of each case is of utmost importance for correct classification. A thorough toxicological analysis of peripheral venous blood and gastric content, as well as a detailed work-up of the death circumstances, are the basis of an exact interpretation of intoxications with DPH.
Journal of Analytical Toxicology, 2002
In this study, regional tissue distributions of the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and its metabolite 3,4-methylenedioxyamphetamine (MDA) in a fatal overdose are presented. Quantitation of MDMA and MDA levels occurred in blood samples taken centrally (right and left heart and main adjacent great vessels) and peripherally (subclavian and femoral blood). In addition, MDMA and MDA concentrations were determined in cardiac and iliopsoas muscle, both lungs, liver, both kidneys, spleen, the four brain lobes, cerebellum and brainstem, and adipose tissue. Finally, MDMA and MDA levels were determined in serum, vitreous humor, urine, and bile. For all samples, a fully validated high-pressure liquid chromatography procedure with fluorescence detection was used.
Journal of Analytical Toxicology, 2014
The codeine to morphine concentration ratio is used in forensic toxicology to assess if codeine has been ingested alone or if morphine and/or heroin have been ingested in addition. In our experience, this interpretation is more difficult in autopsy cases compared with samples from living persons, since high morphine concentrations are observed in cases where only codeine is assumed to have been ingested. We have investigated if codeine and morphine glucuronides are subject to cleavage to the same extent in living and autopsy cases in vitro. We included whole blood samples from eight living subjects and nine forensic autopsy cases, where only codeine ingestion was suspected. All samples were incubated for 2 weeks at 378 8 8 8 8C and analyzed for codeine and six codeine metabolites using liquid chromatography tandem mass spectrometry. A reduction in the codeine to morphine concentration ratio was found, both in samples from living subjects (mean 33%, range 22 -50%) and autopsy cases (mean 37%, range 13 -54%). The increase in the morphine concentrations was greater in the autopsy cases (mean 85%, max 200%) compared with that of the living cases (mean 51%, max 87%). No changes were seen for codeine or codeine-6-glucuronide concentrations. The altered ratios might mislead the forensic toxicologist to suspect morphine or heroin consumption in cases where only codeine has been ingested.
Antemortem and Postmortem Methamphetamine Blood Concentrations: Three Case Reports
Journal of Analytical Toxicology, 2013
We compare antemortem whole-blood to postmortem peripheral blood concentrations of methamphetamine and its metabolite amphetamine in three medical examiner cases. Antemortem specimens, initially screened positive for methamphetamine by ELISA, were subsequently confirmed, together with the postmortem specimens, by GC-MS analysis following solid-phase extraction. Methamphetamine peripheral blood to antemortem blood ratios averaged 1.51 (± 0.049; n = 3) and amphetamine peripheral blood to antemortem blood ratios averaged 1.50 (n = 2). These data show that postmortem redistribution occurs for both methamphetamine and amphetamine, revealing that postmortem blood concentrations are ∼1.5 times greater than antemortem concentrations. Furthermore, as both methamphetamine and amphetamine have previously been shown to have liver/peripheral blood (L/P) ratios of 5-8, it can be proposed that drugs displaying L/P ratios ranging from 5 to 10 may exhibit postmortem concentrations up to twice those concentrations circulating in blood before death.