title: Relationship between methadone and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) in urine samples from Norwegian prisons.
abstract: BACKGROUND
  Methadone maintenance treatment is a widely used therapy in the rehabilitation of opioid addiction the world over. Methadone is metabolised in the body to a number of inactive metabolites, but primarily to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). The Division of Forensic Toxicology and Drug Abuse (DFTDA) of the Norwegian Institute of Public Health carries out drug analysis of urine samples from inmates of prisons throughout Norway. Methadone and EDDP in the urine are also tested for upon request. The results are stored in a secure database at the DFTDA.
  
  
  OBJECTIVE
  The aims of the present study were (1) to observe variations in methadone and EDDP concentrations in urine in relation to urine pH in a large set of urine samples obtained from prison inmates and (2) to analyse samples testing methadone-positive/EDDP-negative and investigate whether such results could occur naturally, without sample tampering.
  
  
  METHODS
  All urine samples that tested positive for methadone over the period 2004-2005 were collected from the DFTDA database, and the relation between methadone and EDDP excretion in urine, and urinary pH was determined. Samples that tested positive for methadone but negative for EDDP were picked out and studied individually.
  
  
  RESULTS
  A total of 1539 urine samples (cases) had tested positive for methadone in our database for the period 2004-2005. There was a strong correlation between the concentration of methadone in urine and urine pH in these samples, with higher concentrations of methadone present at lower pH levels. Cases that tested positive for methadone but negative for EDDP were rare - a total of five (0.3% of all cases tested). These cases were studied in more detail.
  
  
  CONCLUSIONS
  Methadone excretion in urine is dependent on urinary pH. Methadone-positive/EDDP-negative results may suggest sample tampering in some, but not all, cases.
authors.affiliation: Norwegian Institute of Public Health, Division of Forensic Toxicology and Drug Abuse, P.O. Box 4404 Nydalen, 0403, Oslo, Norway. jebe@fhi.no
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bernard
authors.forename: Mimi Stokke
authors.initials: MS
authors.lastname: Opdal
authors.forename: Ritva
authors.initials: R
authors.lastname: Karinen
authors.forename: Jørg
authors.initials: J
authors.lastname: Mørland
authors.forename: Hassan Z
authors.initials: HZ
authors.lastname: Khiabani
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D016903:Drug Monitoring; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008691:Methadone / Q000652:urine*; D008875:Middle Aged; D009294:Narcotics / Q000652:urine*; D009664:Norway; D011330:Prisons; D011759:Pyrrolidines / Q000652:urine*
chemical_list: D015415:Biomarkers; D009294:Narcotics; D011759:Pyrrolidines; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine