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Electrophoresis2014; 35(19); 2863-2869; doi: 10.1002/elps.201400093

Development of a method for analysis of ketamine and norketamine enantiomers in equine brain and cerebrospinal fluid by capillary electrophoresis.

Abstract: Ketamine and norketamine are being transported across the blood brain barrier and are also entering from blood into cerebrospinal fluid (CSF). Enantioselective distributions of these compounds in brain and CSF have never been determined. The enantioselective CE based assay previously developed for equine plasma was adapted to the analysis of these compounds in equine brain via use of an acidic pre-extraction of interferences prior to liquid/liquid extraction at alkaline pH. CSF can be treated as plasma. With 100 mg of brain tissue and 0.5 mL of CSF or plasma, assay conditions for up to 30 nmol/g and 6 μM, respectively, of each enantiomer with LOQs of 0.5 nmol/g and 0.1 μM, respectively, were established and the assays were applied to equine samples. CSF and plasma samples analyzed stemmed from anesthetized patient horses and brain, CSF and plasma were obtained from anesthetized horses that were euthanized with an overdose of pentobarbital. Data obtained indicate that ketamine and norketamine enantiomers are penetrating into brain and CSF with those of ketamine being more favorably transported than norketamine, whereas metabolites of norketamine are hindered. More work is required to properly investigate possible stereoselectivities of the ketamine metabolism and transport of metabolites from blood into brain tissue and CSF.
Publication Date: 2014-07-10 PubMed ID: 24789372DOI: 10.1002/elps.201400093Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research focused on developing a procedure to analyze and measure the distributions of Ketamine and Norketamine compounds in horse brain and spinal fluid, using an adapted version of a previously established capillary electrophoresis based assay. The study found that these compounds enter the brain tissue and spinal fluid more readily than Norketamine metabolites.

Analysis Method of Ketamine and Norketamine Enantiomers

  • Researchers adapted a previously developed enantioselective capillary electrophoresis (CE) assay, suitable for equine plasma, for the analysis of Ketamine and Norketamine in horse brain.
  • An acidic pre-extraction method was used to eliminate interferences before the alkaline pH liquid/liquid extraction.
  • The method allowed assay conditions for each enantiomer with limits of quantification (LOQs).’

Study Design and Sample Collection

  • The study made use of samples from anesthetized horses as well as hose that were euthanized using an overdose of pentobarbital.
  • The obtained samples included brain tissue, cerebrospinal fluid (CSF) and plasma.
  • The method was therefore designed to be applicable to CSF much in the same way it applies to plasma.

Observations and Findings

  • Results indicated that Ketamine and Norketamine enantiomers penetrate into the brain and CSF, but the transport of Ketamine enantiomers was found to be more favored than Norketamine.
  • On the other hand, metabolites of Norketamine faced hindrance.
  • These findings suggest that there may be stereoselective processes involved in the metabolism of Ketamine, as well as the transport of these metabolites from the blood into the brain tissue and CSF.

Future Research

  • The researchers argue that more studies are needed to better understand the potential stereoselectivities of Ketamine’s metabolism and the transport of its metabolites from blood into brain tissue and CSF.

Cite This Article

APA
Theurillat R, Larenza MP, Feige K, Bettschart-Wolfensberger R, Thormann W. (2014). Development of a method for analysis of ketamine and norketamine enantiomers in equine brain and cerebrospinal fluid by capillary electrophoresis. Electrophoresis, 35(19), 2863-2869. https://doi.org/10.1002/elps.201400093

Publication

ISSN: 1522-2683
NlmUniqueID: 8204476
Country: Germany
Language: English
Volume: 35
Issue: 19
Pages: 2863-2869

Researcher Affiliations

Theurillat, Regula
  • Clinical Pharmacology Laboratory, University of Bern, Bern, Switzerland.
Larenza, M Paula
    Feige, Karsten
      Bettschart-Wolfensberger, Regula
        Thormann, Wolfgang

          MeSH Terms

          • Animals
          • Brain Chemistry
          • Electrophoresis, Capillary / methods
          • Horses
          • Ketamine / analogs & derivatives
          • Ketamine / blood
          • Ketamine / cerebrospinal fluid
          • Ketamine / chemistry
          • Ketamine / isolation & purification
          • Reproducibility of Results
          • Sensitivity and Specificity
          • Stereoisomerism

          Citations

          This article has been cited 1 times.
          1. Zhou X, Lv X, Zhang L, Yan J, Hu R, Sun Y, Xi S, Jiang H. Ketamine promotes the neural differentiation of mouse embryonic stem cells by activating mTOR. Mol Med Rep 2020 Jun;21(6):2443-2451.
            doi: 10.3892/mmr.2020.11043pubmed: 32236601google scholar: lookup