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.

journal_name

J Anal Toxicol

authors

Watterson JH,Donohue JP,Betit CC

doi

10.1093/jat/bks045

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

429-33

issue

6

eissn

0146-4760

issn

1945-2403

pii

bks045

journal_volume

36

pub_type

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