title: Concentration ratios of morphine to codeine in blood of impaired drivers as evidence of heroin use and not medication with codeine.
abstract: BACKGROUND
  Both the illicit drug heroin and the prescription drug codeine are metabolized to morphine, which tends to complicate interpretation of opiate-positive samples. We report here the concentrations of morphine and codeine, the morphine/codeine ratios, and 6-acetylmorphine (6-AM) in blood specimens from individuals arrested for driving under the influence of drugs (DUID) in Sweden. The results were compared with positive findings of 6-AM in urine as evidence of heroin intake.
  
  
  METHODS
  In 339 DUID suspects, both blood and urine specimens were available for toxicologic analysis. In another 882 cases, only blood was available. All specimens were initially analyzed by immunoassay, and the positive results were verified by isotope-dilution gas chromatography-mass spectrometry. In routine casework, the limits of quantification (LOQs) for unconjugated opiates were 5 ng/g for blood and 20 microg/L for urine.
  
  
  RESULTS
  The median concentration of morphine in blood was 30 ng/g with 2.5 and 97.5 percentiles of 5 and 230 ng/g, respectively (n = 979). This compares with a median codeine concentration of 20 ng/g and 2.5 and 97.5 percentiles of 5 and 592 ng/g, respectively (n = 784). The specific metabolite of heroin, 6-AM, was identified in only 16 of 675 blood specimens (2.3%). This compares with positive findings of 6-AM in 212 of 339 urine samples (62%) from the same population of DUID suspects. When 6-AM was identified in urine, the morphine/codeine ratio in blood was always greater than unity (median, 6.0; range, 1-66). In 18 instances, 6-AM was present in urine, although morphine and codeine were below the LOQ in blood. The morphine/codeine ratio in blood was greater than unity in 85% of DUID cases when urine was not available (n = 506), and the median morphine and codeine concentrations were 70 ng/g and 10 ng/g, respectively. When morphine/codeine ratios in blood were less than unity (n = 76), the median morphine and codeine concentrations were 10 ng/g and 180 ng/g, respectively.
  
  
  CONCLUSIONS
  Only 2.3% of opiate-positive DUID suspects were verified as heroin users on the basis of positive findings of 6-AM in blood. A much higher proportion (62%) were verified heroin users from 6-AM identified in urine. When urine was not available for analysis, finding a morphine/codeine concentration ratio in blood above unity suggests heroin use and not medication with codeine. This biomarker indicated that 85% of opiate-positive DUID blood samples were from heroin users.
authors.affiliation: Department of Forensic Chemistry, University Hospital, 581 85 Linköping, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Ceder
authors.forename: A W
authors.initials: AW
authors.lastname: Jones
mesh_terms: D001334:Automobile Driving; D003061:Codeine / Q000097:blood* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006556:Heroin Dependence / Q000097:blood* / Q000652:urine; D006801:Humans; D007118:Immunoassay; D009020:Morphine / Q000097:blood* / Q000652:urine; D009022:Morphine Derivatives / Q000097:blood / Q000652:urine; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D009022:Morphine Derivatives; D009020:Morphine; C026979:6-O-monoacetylmorphine; D003061:Codeine