Determination of 3-Phenoxy-N-Methylmorphinan and Metabolites in Plasma

  • J. A. F. de Silva
  • J. Pao
  • M. A. Brooks
Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 12)


The drug (I, Fig. 1) is one of the phenoxymorphinan analogues synthesized by Mohacsi [1] and is under development as a non-narcotic analgesic. It is extensively metabolized in the rat [2] and in the dog [3] 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.


Ether Linkage 111M Phosphate Buffer Dichloromethane Medium Chemical Research Division Peak Monitor 
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Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • J. A. F. de Silva
    • 1
  • J. Pao
    • 1
  • M. A. Brooks
    • 1
  1. 1.Department of Pharmacokinetics and BiopharmaceuticsHoffmann-La Roche Inc.NutleyUSA

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