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 fo 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 β-oxidation of 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.