APPLICATION OF GAS-CHROMATOGRAPHY WITH SELECTIVE DETECTION AND GAS-CHROMATOGRAPHY MASS-SPECTROMETRY TO IDENTIFYING KETAMINE METABOLITES ANDTO EXAMINING THE CONJUGATION OF KETAMINE AND ITS METABOLITES IN HUMANAND RAT ORGANISMS

The metabolism of the anesthetic Ketamine, 2-(2-chlorophenyl)-2-(methy lamino)-cyclohexanone in human and rat organisms was examined by gas c hromatography with nitrogen-phosphorus detection and by gas chromatogr aphy-mass spectrometry. The structure of new Ketamine metabolites (dea minonorketamine and its unsaturated analog, deamino-5,6-dehydronorketa mine) was confirmed. The alternative structures of one of the metaboli tes were found to be -chlorophenyl)-2-(methylamino)-cyclohex-3-ene-1-o l or 6-hydroxy-3,4-dehydronorketamine. The nature of the conjugation o f Ketamine and its metabolites was investigated by the comparison of t he results of acid and enzymatic hydrolysis. In humans, the degree of conjugation of Ketamine and Norketamine in the whole blood and urine v aried within up to 33 and 64% of the total amounts of these substances , respectively. In rats, Ketamine, Norketamine, and dehydronorketamine were excreted with urine primarily in unconjugated forms. Deaminonork etamine was excreted with urine mainly in the conjugated form (the deg ree of conjugation was higher than 80% in both humans and rats). The p resence of O-glycoside bonds in deaminonorketamine conjugates was esta blished. It is likely that O-glucuronides were formed with the enol fo rm of deaminonorketamine; however, the enol form was not detected.