Determination of 3-Phenoxy-N-Methylmorphinan and Metabolites in Plasma
The drug (I, Fig. 1) is one of the phenoxymorphinan analogues synthesized by Mohacsi  and is under development as a non-narcotic analgesic. It is extensively metabolized in the rat  and in the dog  byN-demethylation to form the nor-analogue (I-A),and byp-hydroxylation of the 3-phenoxy ring to yieldI-Band cleavage of the ether linkage to yield the morphinanI-Cand itsN-demethylation produces nor-levorphanol (I-D) (Fig. 1). The presence of four metabolites besides the drug necessitated a strategy for the development of sensitive and specific assays for their quantitation. Of the approaches tried, with dog plasma during pre-clinical drug development, GC-MS (+ve CI) proved the most satisfactory.
KeywordsEther Linkage 111M Phosphate Buffer Dichloromethane Medium Chemical Research Division Peak Monitor
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- 1.Mohacsi, E. (1978 & 1981 ) U.S. Patents 4,113,729 & 4,247,697 resp.Google Scholar
- 2.Kamm, J.J., Szuna, A. & Mohacsi, E. (1979)Pharmacologist21,173 (#156)Google Scholar
- 3.Leinweber, F.-J., Szuna, A.J., Williams, T.H., Sasso, G.J. & De Barbieri, B.A. (1981)Drug Metab. Dispos. 9, 284–291.Google Scholar
- 4.Leinweber, F.-J., Loh, A.C., Carbone, J.J. & Patel, I. H. (1980) Unpublished data on file, Hoffmann-La Roche Inc., Nutley, N.J.Google Scholar
- 7.Dixon, W.R., Crews, T., Mohacsi, E., Inturrisi, C. & Foley, K. (1981)Res. Comm. Chem. Path. Pharmacol. 32, 545–548.Google Scholar
- 9.Min, B.H., Garland, W.A. & Pao, J. (1982) Submitted for publication.Google Scholar