TY - JOUR

T1 - Postmortem Brain-Blood Ratios of Codeine, Fentanyl, Oxycodone and Tramadol

AU - Nedahl, Michael

AU - Johansen, Sys Stybe

AU - Linnet, Kristian

N1 - © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2021/1

Y1 - 2021/1

N2 - 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. 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 chromatography-mass 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 brain-blood 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.

AB - 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. 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 chromatography-mass 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 brain-blood 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.

U2 - 10.1093/jat/bkaa048

DO - 10.1093/jat/bkaa048

M3 - Journal article

C2 - 32390039

VL - 45

SP - 53

EP - 59

JO - Journal of Analytical Toxicology

JF - Journal of Analytical Toxicology

SN - 0146-4760

IS - 1

ER -