Isolation and identification of a new metabolite of naltrexone in human blood and urine.

A new metabolite of naltrexone was isolated from urine and erythrocytes of patients taking 100 mg naltrexone daily. Its tentative structure of 2-hydroxy-3-methoxy naltrexol was derived by analysis of the purified compound using gas chromatography combined with mass spectrometry, high resolution mass spectrometry and infrared spectrometry. Long bioavailability of the new metabolite is indicated by its slower excretion rate into the urine than naltrexone and beta-naltrexol. The rather high concentration of the new metabolite in the erythrocytes and its solubility in non-polar solvents like benzene demonstrate the ability of this compound to penetrate membranes. These features of the new metabolite suggest that it may contribute to naltrexone's long time course of action.