title: Morphine and 6-acetylmorphine concentrations in blood, brain, spinal cord, bone marrow and bone after lethal acute or chronic diacetylmorphine administration to mice.
abstract: The aim of this study was to evaluate postmortem incorporation of opiates in bone and bone marrow after diacetylmorphine (heroin) administration to mice. Mice were given acute (lethal dose of 300 mg/kg) or chronic (10 and 20 mg/kg/24 h for 20 days) intraperitoneal administration of diacetylmorphine. The two metabolites of diacetylmorphine, 6-acetylmorphine (6-AM) and morphine, were extracted from whole blood, brain, spinal cord, bone marrow and bone (after hydrolysis) using a liquid/liquid method. Quantification was performed by gas chromatography-mass spectrometry (GC/MS). Results showed that after acute administration, opiates were present in all studied tissues. Morphine concentrations appeared to be higher than those of 6-AM in blood (52.4 microg/mL versus 27.7 microg/mL, n=12), bone marrow (87.8 ng/mg versus 8.9 ng/mg, n=6) and bone (0.85 ng/mg versus 0.43 ng/mg, n=6), but 6-AM concentrations were higher than those of morphine in brain (14.0 ng/mg versus 7.4 ng/mg, n=12) and spinal cord (27.8 ng/mg versus 20.8 ng/mg, n=12). No correlation was found for both compounds between blood concentrations and either brain, spinal cord, bone or bone marrow concentrations while a significant one was found between brain and spinal cord concentrations either for morphine (r=0.89, n=12, p<0.001) or 6-AM (r=0.93, n=12, p<0.001), the concentration being higher in spinal cord than in brain. When bones were stored for 2 months, only 6-AM remained in bone marrow but not in bone. After chronic administration, mice being sacrificed by cervical dislocation 24 h after the last injection, no opiate was detected in any studied tissues. Further studies are required, in particular in human bones, but these results seem to show that 6-AM could be detect in bone marrow several weeks after the death and could be an alternative tissue for forensic toxicologist to detect a fatal diacetylmorphine overdose, even if no correlation between blood and bone marrow was observed. On the other hand, neither bone tissue nor bone marrow will allow the confirmation of a chronic diacetylmorphine use.
authors.affiliation: Laboratoire de Pharmacologie-Toxicologie, Centre Hospitalier Universitaire Raymond Poincaré, AP-HP, 104 Boulevard R. Poincaré, 92380 Garches, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Guillot
authors.forename: Philippe
authors.initials: P
authors.lastname: de Mazancourt
authors.forename: Michel
authors.initials: M
authors.lastname: Durigon
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Alvarez
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000506:poisoning*; D000818:Animals; D001853:Bone Marrow / Q000737:chemistry; D001842:Bone and Bones / Q000737:chemistry; D001923:Brain Chemistry; D053593:Forensic Toxicology; D008401:Gas Chromatography-Mass Spectrometry; D003932:Heroin / Q000008:administration & dosage* / Q000506:poisoning*; D007274:Injections, Intraperitoneal; D051379:Mice; D009020:Morphine / Q000032:analysis*; D009022:Morphine Derivatives / Q000032:analysis*; D013116:Spinal Cord / Q000737:chemistry
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D003932:Heroin; D009020:Morphine; C026979:6-O-monoacetylmorphine