title: Pharmacokinetics of heroin and its metabolites in vitreous humor and blood in a living pig model.
abstract: Vitreous humor (VH) is an alternative matrix for drug analysis in forensic toxicology. However, little is known about the distribution of xenobiotics, such as opioids, into VH in living organisms. The aim of this study was to simultaneously measure heroin and metabolite concentrations in blood and VH after injection of heroin in a living pig model. Six pigs were under non-opioid anesthesia during the surgical operation and experiment. Ocular microdialysis was used to acquire dialysate from VH, and a venous catheter was used for blood sampling. Twenty milligrams of heroin was injected intravenously with subsequent sampling of blood and dialysate for 6 h. The samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Heroin was not detected in VH; 6-monoacetylmorphine (6-MAM) and morphine were first detected in VH after 60 min. The morphine concentration in VH thereafter increased throughout the experimental period. For 6-MAM,Cmaxwas reached after 230 min in VH. In blood, 6-MAM reachedCmaxafter 0.5 min, with a subsequent biphasic elimination phase. The blood and VH 6-MAM concentrations reached equilibrium after 2 h. In blood, morphine reachedCmaxafter 4.3 min, with a subsequent slower elimination than 6-MAM. The blood and VH morphine concentrations were in equilibrium about 6 h after injection of heroin. In conclusion, both 6-MAM and morphine showed slow transport into VH; detection of 6-MAM in VH did not necessarily reflect a recent intake of heroin. Because postmortem changes are expected to be small in VH, these experimental results could assist the interpretation of heroin deaths.
authors.affiliation: Division of Forensic Medicine, Norwegian Institute of Public Health, Pb 4404 Nydalen, 0403 Oslo, Norway ; Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
authors.forename: André
authors.initials: A
authors.lastname: Gottås
authors.affiliation: Division of Forensic Medicine, Norwegian Institute of Public Health, Pb 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Arnestad
authors.affiliation: The Intervention Centre, Oslo University Hospital, Oslo, Norway.
authors.forename: Per Steinar
authors.initials: PS
authors.lastname: Halvorsen
authors.affiliation: Division of Forensic Medicine, Norwegian Institute of Public Health, Pb 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Liliana C
authors.initials: LC
authors.lastname: Bachs
authors.affiliation: Division of Forensic Medicine, Norwegian Institute of Public Health, Pb 4404 Nydalen, 0403 Oslo, Norway ; Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Høiseth
keywords: 6-MAM; Heroin; Ocular microdialysis; Pharmacokinetic; Pigs; Vitreous humor