Metabolism of cinobufagin in rat liver microsomes. Identification of epimerized and deacetylated metabolites by liquid chromatography/mass spectrometry.
The metabolism of cinobufagin (CB) in rat liver microsomes was studied. By comparison of retention times and fragmentation patterns obtained by thermospray LC/MS with those of authentic standards, four metabolites of CB were also identified, in addition to deacetylCB (M1) and 3-epideacetylCB (M2), which have been reported previously. The additional four metabolites were identified to be 3-epiCB (M4), 3-ketoCB (M5), 3-keto-16 beta-OH-deacetylCB (M3), and 3-keto-16 alpha-OH-deacetylCB (M6). The primary metabolic products of CB were M1 and M2, with a small amount of M4 and trace amounts of M3, M5, and M6. These results indicate that major metabolic routes of CB were deacetylation at the 16-position and epimerization at the 3-position via the 3-keto intermediate.
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
L S
LS
Zhang
T
T
Yoshida
K
K
Aoki
Y
Y
Kuroiwa
D000215:Acylation; D000818:Animals; D002018:Bufanolides / Q000378:metabolism*; D002853:Chromatography, Liquid; D004365:Drugs, Chinese Herbal / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D002018:Bufanolides; D004365:Drugs, Chinese Herbal; C002471:cinobufagin