Stereoselective high-performance liquid chromatographic determination of the enantiomers of ketamine and norketamine in plasma.

An enantioselective high-performance liquid chromatographic assay for the quantitation of the enantiomers of ketamine and its major metabolite norketamine in human plasma is described (assay I). The procedure involved extraction of the compounds from alkalized plasma into cyclohexane. Stereoselective separation was achieved with a prepacked alpha 1-acid glycoprotein column without any derivatization procedure. A second assay using a conventional reversed-phase column to determine total (racemic) ketamine and norketamine is also described. Because of interfering plasma peaks (assay II) the cyclohexane solution was reextracted into 1 M hydrochloric acid. The detection wavelength was 215 nm for all substances. The limit of quantification of the method was ca. 40 ng/ml in plasma. The assays were sensitive and reproducible. The method was demonstrated to be sensitive for stereoselective pharmacokinetic studies of ketamine after clinical doses.

[1]  J. Hermansson.  Direct liquid chromatographic resolution of racemic drugs by means of α1-acid glycoprotein as the chiral complexing agent in the mobile phase , 1984 .

[2]  E F Domino,et al.  Dissociative Anesthesia: Further Pharmacologic Studies and First Clinical Experience with the Phencyclidine Derivative Cl‐581 , 1966, Anesthesia and analgesia.

[3]  M. Kochhar.  The identification of ketamine and its metabolites in biologic fluids by gas-chromatography-mass spectrometry. , 1977, Clinical toxicology.

[4]  A. Glazko,et al.  Biotransformation and Disposition of Ketamine , 1974, International anesthesiology clinics.

[5]  L. Needham,et al.  Determination of ketamine and some in vivo metabolites using high-pressure liquid chromatography. , 1975, Journal of chromatography.

[6]  D. Reich,et al.  Ketamine: an update on the first twenty-five years of clinical experience , 1989, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[7]  J. Adams,et al.  Biotransformation of ketamine, (Z)-6-hydroxyketamine, and (E)-6-hydroxyketamine by rat, rabbit, and human liver microsomal preparations. , 1987, Xenobiotica; the fate of foreign compounds in biological systems.

[8]  J. Hermansson.  Enantiomeric separation of drugs and related compounds based on their interaction with α1-acid glycoprotein , 1989 .

[9]  P. White,et al.  Ketamine--its pharmacology and therapeutic uses. , 1982, Anesthesiology.

[10]  S. Björkman.  Determination of the enantiomers of ketoprofen in blood plasma by ion-pair extraction and high-performance liquid chromatography of leucinamide derivatives. , 1987, Journal of chromatography.

[11]  J. Adams,et al.  Derivatization of chiral amines with (S,S)-N-trifluoroacetylproline anhydride for GC estimation of enantiomeric composition. , 1982, Journal of pharmaceutical sciences.

[12]  M. Cohen,et al.  Distribution in the Brain and Metabolism of Ketamine in the Rat after Intravenous Administration , 1973, Anesthesiology.

[13]  P. White,et al.  Pharmacology of Ketamine Isomers in Surgical Patients , 1980, Anesthesiology.

[14]  A. Glazko,et al.  A gas chromatographic assay for ketamine in human plasma. , 1972, Anesthesiology.

[15]  E. Domino,et al.  Plasma Levels of Ketamine and Two of Its Metabolites in Surgical Patients Using a Gas Chromatographic Mass Fragmentographic Assay , 1982, Anesthesia and analgesia.

[16]  E. Ariëns.  Stereochemistry: A source of problems in medicinal chemistry , 1986, Medicinal research reviews.

[17]  W. L. Way,et al.  Comparative pharmacology of the optical isomers of ketamine in mice. , 1978, European journal of pharmacology.