Comparison of Relative Distribution of Ketamine and Norketamine in Decomposed Skeletal Tissues Following Single and Repeated Exposures

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 7...

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Bibliographic Details
Published in:Journal of analytical toxicology 2012-07, Vol.36 (6), p.429-433
Main Authors: Watterson, James H., Donohue, Joseph P., Betit, Caroline C.
Format: Article
Language:English
Subjects:
Algorithms
Anesthetics, General - administration & dosage
Anesthetics, General - analysis
Anesthetics, General - pharmacokinetics
Animals
Biotransformation
Bone and Bones - chemistry
Dose-Response Relationship, Drug
Forensic Toxicology - methods
Gas Chromatography-Mass Spectrometry
Injections, Intraperitoneal
Ketamine - administration & dosage
Ketamine - analogs & derivatives
Ketamine - analysis
Ketamine - pharmacokinetics
Male
Organ Specificity
Postmortem Changes
Rats
Rats, Wistar
Solid Phase Extraction
Tissue Distribution
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Summary: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.
ISSN:0146-4760
1945-2403
DOI:10.1093/jat/bks045