Enantioselective capillary electrophoresis with sulfated cyclodextrins for monitoring ketamine and its metabolites in biosamples and its application to assess metabolic steps and kinetic parameters

• Monitoring of ketamine and metabolites by enantioselective CE in biosamples. • Sulfated β- and γ-cyclodextrins for stereoselective analysis of ketamine metabolites. • Identification of cytochrome P450 enzymes involved in ketamine metabolism in vitro. • Stereoselective pathways and pharmacokinetics of ketamine in equines and canines. • Inhibition of ketamine metabolism in equines and canines. Sulfated cyclodextrin based enantioselective capillary electrophoresis for the monitoring of the stereoisomers of ketamine and its metabolites norketamine, 5,6-dehydronorketamine and hydroxynorketamine in biosamples is reviewed. A survey of reported assays with their specifications is presented together with their limitations in terms of distinguishing between the various hydroxynorketamine stereoisomers formed in vitro and in vivo. Applications discussed include (i) the identification of single cytochrome P450 enzymes that are involved in the various metabolic steps in humans, equines and canines, (ii) the assessment of the metabolic patterns present after incubation of ketamine or norketamine with liver microsomes of different species, (iii) the quantitation of an in vitro metabolic step in absence and presence of an inhibitor, (iv) the monitoring of the stereoisomers of ketamine and its metabolites in urine, plasma, cerebrospinal fluid, brain and hair, and (v) the pharmacokinetics of ketamine and norketamine enantiomers after bolus application, target control infusion or low-dose, subanesthetic constant rate infusion of racemic ketamine and S-ketamine to equines and canines. The reviewed metabolic ketamine work assessed by enantioselective capillary electrophoresis provides insight into the stereoselectivity of the metabolic pathways of ketamine and improved infusion, anesthetic and antinociceptive application schemes of racemic ketamine and S-ketamine in veterinary medicine.