title: Comparison of relative distribution of ketamine and norketamine in decomposed skeletal tissues following single and repeated exposures.
abstract: Bone was analyzed for ketamine and norketamine to examine whether different patterns of drug exposure could be discriminated. Rats received (intraperitoneally) one 75 mg/kg dose (Acute-1 and Acute-2 groups), three 25-mg/kg doses 1 hour apart (Repeated group), or nine single daily ketamine doses of 75 mg/kg followed by a 24-h washout period (Chronic group). Following euthanasia, all animals decomposed to skeleton outdoors. Ground samples of recovered bone underwent methanolic extraction and analysis by gas chromatography-mass spectrometry after solid-phase extraction. Drug levels (mass normalized response ratios) were compared across bone types and exposure pattern. Bone type significantly influenced drug level for the Acute-1 and Repeated dose groups, and the drug/metabolite level ratio (DMLR) for the Acute-1 group. Mean ketamine and norketamine level and DMLR varied by up to 8-fold, 7-fold and 3-fold, respectively, in the Acute-1 group, and by up to 24-fold, 5-fold and 10-fold, respectively, in the Repeated group. Drug level and DMLR differed significantly between the Acute-1 and Repeated groups for most bone types. In the Chronic group, only 1/16 and 4/16 samples were positive for ketamine and norketamine, respectively. All Acute-2 samples were positive for ketamine and norketamine. The Acute-2 and Chronic groups differed significantly in ketamine and norketamine levels, and DMLR.
authors.affiliation: Department of Forensic Science, Laurentian University, 935 Ramsey Lake Rd., Sudbury, Ontario, Canada. jwatterson@laurentian.ca
authors.forename: James H
authors.initials: JH
authors.lastname: Watterson
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Donohue
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Betit
mesh_terms: D000465:Algorithms; D018681:Anesthetics, General / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D001842:Bone and Bones / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D053593:Forensic Toxicology / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry; D007274:Injections, Intraperitoneal; D007649:Ketamine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics*; D008297:Male; D009928:Organ Specificity; D011180:Postmortem Changes; D051381:Rats; D017208:Rats, Wistar; D052616:Solid Phase Extraction; D014018:Tissue Distribution
chemical_list: D018681:Anesthetics, General; D007649:Ketamine; C033419:norketamine