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Metabolism of the enantiomers of 2‐hydroxy‐ N ‐cyclopropylmethylmorphinan in dog and man
Author(s) -
Vane F. M.,
Ellis D. H.,
Rao J.,
Petrin M.,
Blount J. F.,
Mohacsi E.,
Szuna A.,
Kamm J. J.
Publication year - 1978
Publication title -
biomedical mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0306-042X
DOI - 10.1002/bms.1200050808
Subject(s) - enantiomer , metabolism , chemistry , stereochemistry , biochemistry
The major metabolic pathway of the (−) enantiomer and the (+) enantiomer of 2‐hydroxy‐ N ‐cyclopropylmethylmorphinan in dogs was shown to be conjugation with glucuronic acid and/or sulfate. Gas chromatography mass spectrometry, nuclear magnetic resonance spectroscopy and X‐ray crystallography were used to identify additional metabolites of the two enantiomers in dog urine after hydrolysis with Glusulase. Metabolites of the (−) enantiomer were identified as 2‐hydroxymorphinan and 2,7β‐dihydroxy‐ N ‐cyclopropropylmethylmorphinan. The major metabolites of the (+) enantiomer in hydrolyzed dog urine were identified as 2‐hydroxymorphinan, 2,3‐dihydroxy‐ N ‐cyclopropylmethylmorphinan and 2‐methoxy‐3‐hydroxy‐ N ‐cyclopropylmethylmorphinan. In addition, tentative or partial structures were postulated for three minor metabolites of the (+) enantiomer: 2‐methoxy‐3‐hydroxymorphinan, a metabolite containing a hydroxyl group on either carbon 4, 5, 6 or 7 and a methylated catechol metabolite containing a hydroxyl group on carbon 4, 5, 6 or 7. Thus, the major oxidative pathways of the (−) enantiomer were N ‐dealkylation and aliphatic hydroxylation, while the (+) enantiomer mainly underwent N ‐dealkylation and aromatic hydroxylation, followed by phenolic methylation. Analysis of urine from a human subject administered the (−) enantiomer suggested that the metabolism of this isomer by man was similar to its metabolism by dog.