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Methadone and methadone metabolites in postmortem specimens.

Terry J Danielson1, Ashraf Mozayani, Luis A Sanchez

  • 1Harris County Medical Examiner, 1885 Old Spanish Trail, Houston, TX, 77054, USA.

Forensic Science, Medicine, and Pathology
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Summary

This study measured methadone (METH) and its metabolites EDDP and EMDP in postmortem tissues. EMDP accumulation in liver tissue was found to be highly individual, suggesting variable in vivo conversion.

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Area of Science:

  • Forensic Toxicology
  • Pharmacokinetics
  • Analytical Chemistry

Background:

  • Methadone (METH) is a widely used opioid medication.
  • Understanding METH metabolism is crucial for interpreting postmortem toxicology results.
  • Individual variations in drug metabolism can impact tissue concentrations.

Purpose of the Study:

  • To quantify methadone (METH) and its metabolites, EDDP and EMDP, in postmortem blood and liver.
  • To investigate the relationship between METH, EDDP, and EMDP concentrations in postmortem specimens.
  • To explore the in vivo conversion efficiency and postmortem accumulation patterns of EMDP.

Main Methods:

  • Liquid chromatography/tandem mass spectrometry (LC/MS/MS) was utilized for drug quantification.
  • Deuterated internal standards and multiple reaction monitoring (MRM) enhanced assay accuracy.
  • Analysis was performed on peripheral blood and liver tissue from 46 methadone-positive cases.

Main Results:

  • Methadone (METH) and EDDP were consistently detected in all postmortem blood and liver samples.
  • EMDP was detected in liver tissue of only 17 cases, at significantly lower concentrations than EDDP.
  • METH and EDDP concentrations in EMDP-positive cases overlapped with, but were generally higher than, those in EMDP-negative cases.

Conclusions:

  • Methadone (METH) is efficiently converted to EDDP in vivo.
  • In vivo conversion of METH to EMDP appears less efficient, leading to variable postmortem accumulation.
  • Individual metabolic pathways significantly influence EMDP levels in postmortem tissues.