Isolation and stereochemical identification of a metabolite of naltrexone from human urine / Nithiananda Chatterjie, James M. Fujimoto, Charles E. Inturrisi, Sandra Reorig, Richard I.H. Wang, David V. Bowen, Frank H. Field, and Donald D. Clarke Department of Pharmacology, Cornell University Medical College (N.C., C.E.I.), Department of Pharmacology, Medical College of Wisconsin (J.M.F., S.R.), Veterans Administrative Center, Wood, Wisconsin (R.I.H.W.), Mass Spectrometry Service Laboratory, The Rockefeller University (D.V.B., F.H.F.), and Department of Chemistry, Fordham University (D.D.C.)

Abstract

Pooled urine samples from patients receiving 100-200 mg of naltrexone per day orally were extracted; the basic (alkaloid) compounds derived were isolated by preparative thin-layer chromatography. The major metabolite of naltrexone was found to be an epimer of N-cyclopropylmethyl- 14-hydroxy-7,8-dihydronormorphine wherein the 6-keto group of naltrexone had been reduced to yield the 6β-hydroxy epimer (an isomorphine). This conclusion was based on infrared, mass, and nuclear magnetic resonance spectra studies. Furthermore, the reduction product formed in vitro in a soluble chicken liver enzyme system from naltrexone and an in vivo metabolite of naloxone derived from the chicken were found to have the more commonly expected 6α-hydroxy orientatio