Separation of hydroxynorketamine stereoisomers using capillary electrophoresis with sulfated β-cyclodextrin and highly sulfated γ-cyclodextrin.

Sandbaumhüter, Friederike Andrea; Theurillat, Regula; Thormann, Wolfgang (2017). Separation of hydroxynorketamine stereoisomers using capillary electrophoresis with sulfated β-cyclodextrin and highly sulfated γ-cyclodextrin. Electrophoresis, 38(15), pp. 1878-1885. Wiley-VCH 10.1002/elps.201700016

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The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α7 -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed. The assay is based on liquid/liquid extraction of the analytes from the biological matrix, electrokinetic sample injection across a buffer plug and analysis of the stereoisomers in a phosphate background electrolyte (BGE) at pH 3 comprising a mixture of sulfated β-cyclodextrin (5 mg/mL) and highly sulfated γ-cyclodextrin (0.1%). The method was used to analyze samples of an in vitro study in which ketamine was incubated with equine liver microsomes and in plasma samples of dogs and horses that were collected after an i.v. bolus injection of racemic ketamine.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Laboratory for Clinical Pharmacology

UniBE Contributor:

Sandbaumhüter, Friederike Andrea; Theurillat, Regula and Thormann, Wolfgang

ISSN:

0173-0835

Publisher:

Wiley-VCH

Language:

English

Submitter:

Wolfgang Thormann

Date Deposited:

21 Feb 2018 09:04

Last Modified:

28 Oct 2019 15:45

Publisher DOI:

10.1002/elps.201700016

PubMed ID:

28213944

Uncontrolled Keywords:

Capillary electrophoresis Equine liver microsomes Hydroxynorketamine Ketamine Stereoisomer

BORIS DOI:

10.7892/boris.108292

URI:

https://boris.unibe.ch/id/eprint/108292

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