Metabolism of idebenone (CV-2619), a new cerebral metabolism improving agent: isolation and identification of metabolites in the rat and dog.
Metabolic studies of idebenone (CV-2619), a new cerebral metabolism improving agent, in the rat and dog by thin-layer chromatography, gas-liquid chromatography-mass spectrometry and fast atom bombardment-mass spectrometry led to characterization of the following metabolites: the parent compound, 6-(9-carboxynonyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (QS-10), 6-(7-carboxyheptyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (QS-8), 6-(5-carboxypentyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (QS-6), 6-(3-carboxypropyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (QS-4), 1- or 4-phenyl sulfate of the hydroquinone derivatives of CV-2619 and QS-4, and 1- and 4-phenyl glucuronides of the hydroquinone derivative of QS-10. These results indicated that CV-2619 was metabolized by oxidation of the side chain followed by beta-oxidation to form successively QS-10, QS-8, QS-6 and QS-4, and reduction of the quinone ring and subsequent conjugation yielding the sulfates and glucuronides of the hydroquinone derivatives of CV-2619, QS-10, QS-8, QS-6 and QS-4.
D000818:Animals; D016227:Benzoquinones; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004285:Dogs; D005965:Glucuronates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D011809:Quinones / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D005965:Glucuronates; D011809:Quinones; D014451:Ubiquinone; C036619:idebenone