Abstract
Two new metabolites of daunomycin have been identified as 8-(1-hydroxyethyl)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5, 12-naphthacenedione (Dx, I) and 8-acetyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5, 12-naphthacenedione (Dy, II). Two similar metabolites of adriamycin have been identified as 8-hydroxyacetyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5, 12-napthacenedione (Ay, IV) and 8-(1,2-dihydroxyethyl)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5, 12-napthacenedione (Ax, V), characterized as its diacetate (III). These metabolites arise by an unusual reductive cleavage of the O-glycosidic linkage of the parent drugs. The metabolites have been identified by application of infrared spectroscopy, high resolution mass spectroscopy and, in two cases, Fourier transform proton magnetic resonance spectroscopy. The latter technique appears to be a sensitive and useful adjunct to mass spectroscopy in structure elucidation of drug metabolites.
Footnotes
- Received November 19, 1971.
- Accepted April 4, 1972.
- © 1972, by The Williams & Wilkins Company
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
