Application of gas chromatography with selective detection and gas chromatography-mass spectrometry to identifying Ketamine metabolites and to examining the conjugation of Ketamine and its metabolites in human and rat organisms

摘要

The metabolism of the anesthetic Ketamine, 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone, in human and rat organisms was examined by gas chromatography with flame-ionization and nitrogen-phosphorus detection and by gas chromatography-mass spectrometry. The structure of new Ketamine metabolites (deaminonorketamine and its unsaturated analog, deamino-5,6--dehydronorketamine) was confirmed. The alternative structures of one of the metabolites were found to be 2-(2-chlorophenyl)-2-(methylamino)-cyclohex-3-ene-1- ol or 6-hydroxy-3,4-dehydronorketamine. The nature of conjugation of Ketamine and its metabolites was determined by the comparison of the results of acid and enzymatic hydrolysis. In human beings, the degree of conjugation of Ketamine and Norketamine in the whole blood and urine varied 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. Deaminonorketamine was excreted with urine mainly in the conjugated form (the degree of conjugation was higher than 80% in both humans and rots). The presence of O-glycoside bonds in deaminonorketamine conjugates was established. It is likely that O-glucuronides were formed with the enol form of deaminonorketamine; however, the enol form was not detected.