Norketamine and ketamine

Moore, K.A., Skierov, J., Levine, B., and Jacobs, A.J., Urine concentrations of ketamine and norketamine following illegal consumption, J. Anal. Toxicol., 25, 583-588, 2001. 

Williams and Wainer (2002) use examples of two chiral separations to demonstrate their utility in research. In one example, the difference between enantiomers in the competitive displacement of cyclosporine from immobilized P-glycoprotein was studied. In the other, the pharmacokinetic profiles of (+) and (—)-ketamine and (-h) and (—)-norketamine were determined (Williams and Wainer, 2002). 

Ketamine, a general anesthetic producing hallucinations and exhibiting an addiction potential, and norketamine have been determined in urine using SPE combined with RPLC-ESI(+)-MS-MS [49]. Cheng and Mok [49] developed a fast HPLC-MS-MS method able to separate and detect ketamine in a 2.5 min chromatographic run with a LOD of 5ng/mL. The method was applied to routine ketamine urine screening to a maximum of 200 samples per day. 

Disposition in the Body. Rapidly distributed in the tissues following parenteral administration. About 90% of a dose is excreted in the urine in 72 hours, with about 2% of the dose as unchanged drug, 2% as norketamine, 16% as dehydronorke-tamine, and 80% as conjugates of hydroxylated metabolites. Norketamine (which has about one-sixth of the potency of ketamine) and dehydronorketamine are found in the serum in concentrations similar to those of ketamine. It has been suggested that dehydronorketamine may be an analytical artefact rather than a metabolite. 

Separation of the enantiomers of ketamine metabolites, norketamine and dehydroketamine... 

Ketamine and its Metabolites Norketamine and Dehydro-norketamine Courtesy of ASTEC Inc. 

Also the metabolite dehydronorketamine has a longer duration time in urine than its precursor ketamine and the other metabolite norketamine. Dehydronorketamine can be detected after 7-10 days from the consumption of a modest dose of ketamine and is therefore a very useful diagnostic metaboUte. 

Ketamine is metabolized primarily in the liver region leading to the formation of two main compounds norketamine (NK) and dehydronorketamine (DHNK). NK, a compound much less powerful than the substance itself, is achieved through the demethylation, subsequent dehydrogenation generates DHNK [27, 28],... 

Ketamine undergoes hepatic biotransformation in the horse. The primary metabolites are norketamine and dehydronorketamine (Delatour et al 1991, Sams Pizzo 1987, Seay et al 1993). Up to 40% of ketamine can be excreted unchanged in the urine. Upon recovery from ketamine anesthesia, 40% of the ketamine dose still remains in the horse at levels insufficient to produce anesthesia (Kaka et al 1979). In the horse, the elimination half-life of ketamine is reported to be 42-65 min with a total body clearance of 23-26 ml/kg/min (Kaka et al 1979, Waterman et al 1987). 

The initial screening test for PCP is typically immunoassay. For confirmation of a presumptive positive test, a quantitative drug measurement is performed using GC-MS. Immunoassays for ketamine are not avaEable. Ketamine, norketamine, and dehydronorketamine may be determined by GC-MS or LC-MS. ... 

Ketamine is hepatically metabolized to norketamine, which has reduced CNS activity norketamine is fnrther metabolized and excreted in urine and bile. Ketamine has a large volume of distribution and rapid clearance that make it snitable for continuous infusion withont the drastic lengthening in duration of action seen with thiopental. Protein binding is much lower with ketamine than with the other parenteral anesthetics. 

Ketamine, norketamine, and dehydronoiicetamine were extracted from plasma and separated on a C]g column (2 = 210nm) using a 77/23 water (30 mM phosphate at pH 7.2)/acetonitrile mobile phase [1468]. Baseline resolution, excellent peak shapes, and total elution in 18 min were achieved. The linear ranges were reported as 5-5000 pg/L and the quantitation limit as 5 pg/L. 

Ketamine is extensively metabolized in the liver via N-demethylation via the cytochrome P450 system to yield norketamine. This metabohte has one-third the activity of the parent compound, and is subsequently hydroxylated and conjugated to become a... 

Leung and Baillie [10] studied the stereoselective metabolism of NK in rat liver microsomes using racemic NK and its individual enantiomers (/ -NK and (5) -NK labeled with deuterium on aromatic ring ((. -NK-Dz). Ketamine was used as internal standard and NK and its metabolites were analyzed after PFP derivati-zation as mono or bis PFP derivatives, respectively. They have assessed the production of 4 and 6 hydroxy norketamine (4-OH-NK, 6-OH-NK) by monitoring the two fragment ions at m/z 304 and 306, which correspond to unlabeled and dideuterated NK, respectively. Norketamine was monitored by two fragment ions at m/z 306 and 308 for the unlabeled (./ -enantiomer and the (. -labeled enantiomer, respectively. Norketamine was shown to exhibit stereoselective metabolism since 6 OH NK was preferentially obtained from (. NK, and 4-OH-NK was preferentially obtained from (./ -NK. 

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