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The metabolism of CGS—15873 in man using stable isotope pattern recognition techniques
Author(s) -
Leal M.,
Hayes M. J.,
Powell M. L.
Publication year - 1992
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510130807
Subject(s) - metabolite , derivatization , autoreceptor , chemistry , thermospray , urine , glucuronide , chromatography , agonist , metabolism , conjugate , dopamine , pharmacology , tandem mass spectrometry , mass spectrometry , biochemistry , endocrinology , biology , selected reaction monitoring , receptor , mathematical analysis , mathematics
CGS 15873 is a relatively specific dopamine agonist with preferential activity at the presynaptic autoreceptor and therefore may represent a novel agent for the treatment of schizophrenia and/or Parkinson's disease. Several metabolites have been identified in the rat and monkey using an isotopically enriched dosing solution and pattern recognition techniques coupled with GC/MS and LC/MS. In this study, the metabolism of CGS 15873 was investigated in man using these same techniques. In urine, specific isotope clusters were found that matched the dosing solution pattern. Three metabolites were identified: an O‐glucuronide conjugate of the parent drug, N‐despropyl CGS 15873, and a keto metabolite of CGS 15873. Thermospray LC/MS allowed for the direct confirmation of the conjugated metabolite. GC/MS required derivatization but afforded greater sensitivity compared to LC/MS.