Characterization of the stereoselective biotransformation of ketamine to norketamine via determination of their enantiomers in equine plasma by capillary electrophoresis.
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.
Theurillat
Regula
R
Department of Clinical Pharmacology, University of Bern, Bern, Switzerland.
Knobloch
Monika
M
Levionnois
Olivier
O
Larenza
Paula
P
Mevissen
Meike
M
Thormann
Wolfgang
W
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
D000777:Anesthetics; D007649:Ketamine; C033419:norketamine