title: Characterization of the stereoselective biotransformation of ketamine to norketamine via determination of their enantiomers in equine plasma by capillary electrophoresis.
abstract: A robust CE method for the simultaneous determination of the enantiomers of ketamine and norketamine in equine plasma is described. It is based upon liquid-liquid extraction of ketamine and norketamine at alkaline pH from 1 mL plasma followed by analysis of the reconstituted extract by CE in the presence of a pH 2.5 Tris-phosphate buffer containing 10 mg/mL highly sulfated beta-CD as chiral selector. Enantiomer plasma levels between 0.04 and 2.5 microg/mL are shown to provide linear calibration graphs. Intraday and interday precisions evaluated from peak area ratios (n = 5) at the lowest calibrator concentration are < 8 and < 14%, respectively. The LOD for all enantiomers is 0.01 microg/mL. After i.v. bolus administration of 2.2 mg/kg racemic ketamine, the assay is demonstrated to provide reliable data for plasma samples of ponies under isoflurane anesthesia, of ponies premedicated with xylazine, and of one horse that received romifidine, L-methadone, guaifenisine, and isoflurane. In animals not premedicated with xylazine, the ketamine N-demethylation is demonstrated to be enantioselective. The concentrations of the two ketamine enantiomers in plasma are equal whereas S-norketamine is found in a larger amount than R-norketamine. In the group receiving xylazine, data obtained do not reveal this stereoselectivity.
authors.affiliation: Department of Clinical Pharmacology, University of Bern, Bern, Switzerland.
authors.forename: Regula
authors.initials: R
authors.lastname: Theurillat
authors.forename: Monika
authors.initials: M
authors.lastname: Knobloch
authors.forename: Olivier
authors.initials: O
authors.lastname: Levionnois
authors.forename: Paula
authors.initials: P
authors.lastname: Larenza
authors.forename: Meike
authors.initials: M
authors.lastname: Mevissen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
mesh_terms: D000777:Anesthetics / Q000097:blood; D000818:Animals; D001711:Biotransformation; D002138:Calibration; D004347:Drug Interactions; D006736:Horses; D007649:Ketamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D000777:Anesthetics; D007649:Ketamine; C033419:norketamine