title: Evaluation of metabolite/drug ratios in blood and urine as a tool for confirmation of a reduced tolerance in methadone-related deaths in Denmark.
abstract: BACKGROUND
  Methadone blood concentrations in fatal cases are highly variable and there is an appreciable overlap between therapeutic methadone concentrations and the concentrations detected in fatalities. As with other opioids, the background of these methadone-related deaths is unclear. The aim of this study was to investigate if short-time abstinence was contributing to the cause of death in methadone-related deaths by evaluation of the EDDP/methadone ratio in blood and urine.
  
  
  METHODS
  Samples of blood and urine were collected from 103 autopsy cases and analysed for the concentrations of methadone and its main metabolite EDDP. The cases were divided into three groups according to the cause of death: cases where methadone was the cause of death (N=67), cases where poly-drug poisoning including methadone was the cause of death (N=24) and cases where death were caused by other factors (N=12). Urine samples from 11 living persons receiving methadone were also included.
  
  
  RESULTS
  In general, a substantial overlap of the methadone concentrations in blood and urine was seen between the groups. There was a tendency of lower median EDDP/methadone urinary ratios in the methadone poisoning group (median: 1.0), poly-drug poisoning group (median: 0.94) and in the fatalities not related to methadone (median: 1.1) compared to the living subjects in methadone treatment (median: 1.6), although the differences were not significant.
  
  
  CONCLUSIONS
  It was not possible to reveal a possible abstinence period prior to death by using the EDDP/methadone ratio in blood and urine in methadone-related deaths.
authors.affiliation: Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health Sciences, University of Copenhagen, Frederik V's vej 11, DK-2100, Denmark. Electronic address: marie.nielsen@sund.ku.dk.
authors.forename: Marie K K
authors.initials: MK
authors.lastname: Nielsen
authors.forename: Sys S
authors.initials: SS
authors.lastname: Johansen
authors.forename: Kristian
authors.initials: K
authors.lastname: Linnet
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D003718:Denmark / Q000453:epidemiology; D062787:Drug Overdose; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000009:adverse effects* / Q000378:metabolism*; D008875:Middle Aged; D009294:Narcotics / Q000009:adverse effects* / Q000378:metabolism*; D009293:Opioid-Related Disorders / Q000401:mortality* / Q000534:rehabilitation*; D011759:Pyrrolidines / Q000097:blood / Q000652:urine; D013237:Stereoisomerism; D055815:Young Adult
chemical_list: D009294:Narcotics; D011759:Pyrrolidines; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
keywords: Chiral liquid chromatography–tandem mass spectrometry; Drug addicts; Forensic toxicology; Poisoning; Postmortem biological matrices; R/S-methadone