title: Deuterodiacetylmorphine as a marker for use of illicit heroin by addicts in a heroin-assisted treatment program.
abstract: In preparation for a treatment program concerning the medical coprescription of heroin and methadone to treatment-resistant addicts in the Netherlands, we studied a novel strategy for monitoring co-use of illicit (nonprescribed) heroin. A deuterated analogue of heroin was added (1:20) to pharmaceutical, smokable heroin (a powder mixture of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate), to be used by inhalation after volatilization ("chasing the dragon"). Plasma and urine samples were collected from nine male patients who had used pharmaceutical, smokable heroin during a four-day stay in a closed clinical research unit, and these samples were analyzed by liquid chromatography coupled with tandem mass spectrometry. Ratios of deuterated and undeuterated diacetylmorphine and 6-acetylmorphine (MAM/MAM-d3) in plasma and urine were calculated from peak areas of these substances in the respective chromatograms. The MAM/MAM-d3 ratios in plasma and urine were normally distributed (with small standard deviations) and independent from concentrations of 6-acetylmorphine and from time after use of pharmaceutical heroin. A MAM/MAM-d3 ratio in urine above 32.8 was considered indicative of co-use of illicit heroin, and this value was associated with a false-positive rate of only 1% (95% confidence interval: -1 to 3%). The MAM/MAM-d3 ratio was detectable in urine for 4-9.5 h after use of pharmaceutical, smokable heroin. Addition of stable, isotopically labelled heroin to pharmaceutical, smokable heroin is considered to be a feasible strategy for the detection of co-use of illicit heroin by patients in heroin-assisted treatment.
authors.affiliation: Slotervaart Hospital, Department of Pharmacy and Pharmacology, Amsterdam, The Netherlands. apmlk@slz.nl
authors.forename: Marjolein G
authors.initials: MG
authors.lastname: Klous
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Rook
authors.forename: Michel J X
authors.initials: MJ
authors.lastname: Hillebrand
authors.forename: Wim
authors.initials: W
authors.lastname: van den Brink
authors.forename: Jan M
authors.initials: JM
authors.lastname: van Ree
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000280:Administration, Inhalation; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002853:Chromatography, Liquid; D003932:Heroin / Q000008:administration & dosage / Q000097:blood / Q000652:urine; D006556:Heroin Dependence / Q000097:blood / Q000534:rehabilitation* / Q000652:urine; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D012015:Reference Standards; D012680:Sensitivity and Specificity; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D015415:Biomarkers; D003932:Heroin