title: Morphine to codeine concentration ratio in blood and urine as a marker of illicit heroin use in forensic autopsy samples.
abstract: A morphine to codeine ratio greater than unity (M/C>1) has been suggested as an indicator of heroin use in living individuals. The aim of this study was to examine the morphine to codeine ratio in a large population (N=2438) of forensically examined autopsy cases positive for 6-monoacetylmorphine (6-MAM) and/or morphine in blood and/or urine. Blood and urine concentrations of 6-MAM, morphine and codeine were examined using GC-MS and LC-MS/MS methods. In 6-MAM positive samples, the M/C ratio was greater than unity in 98% (N=917) of the blood samples and 96% (N=665) of the urine samples. Stratification of 6-MAM negative cases by M/C above or below unity revealed similarities in morphine and codeine concentrations in cases where M/C>1 and 6-MAM positive cases. Median blood and urine morphine concentrations were 8-10 times greater than codeine for both groups. Similarly to 6-MAM positive cases, 25-44 year-old men prevailed in the M/C>1 group. In comparison to cases where M/C ≤ 1, the M/C ratio was a hundred times higher in both 6-MAM positive and M/C>1 cases. The range of morphine concentration between the lowest and the highest quintile of codeine in M/C>1 cases was similar to that in 6-MAM positive cases. This range was much higher than for M/C ≤ 1 cases. Moreover, linear regression analyses, adjusted for age and gender, revealed a strong positive association between morphine and codeine in 6-MAM positive and M/C>1 cases. The M/C ratio appeared to be a good marker of heroin use in post-mortem cases. Both blood and urine M/C>1 can be used to separate heroin users from other cases positive for morphine and codeine.
authors.affiliation: Norwegian Institute of Public Health, Division of Forensic Medicine and Drug Abuse, Lovisenberggata 6, P.O. Box 4404, Nydalen, 0403 Oslo, Norway. svetlana.konstantinova@fhi.no
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Konstantinova
authors.forename: Per T
authors.initials: PT
authors.lastname: Normann
authors.forename: Marianne
authors.initials: M
authors.lastname: Arnestad
authors.forename: Ritva
authors.initials: R
authors.lastname: Karinen
authors.forename: Asbjørg S
authors.initials: AS
authors.lastname: Christophersen
authors.forename: Jørg
authors.initials: J
authors.lastname: Mørland
mesh_terms: D000293:Adolescent; D000328:Adult; D003061:Codeine / Q000097:blood* / Q000652:urine*; D005260:Female; D053593:Forensic Toxicology; D008401:Gas Chromatography-Mass Spectrometry; D006556:Heroin Dependence / Q000175:diagnosis*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood* / Q000652:urine*; D009022:Morphine Derivatives / Q000097:blood / Q000652:urine; D009294:Narcotics / Q000097:blood / Q000652:urine; D015813:Substance Abuse Detection; D055815:Young Adult
chemical_list: D009022:Morphine Derivatives; D009294:Narcotics; D009020:Morphine; C026979:6-O-monoacetylmorphine; D003061:Codeine