Affiliations: Eisai Research Laboratories, Eisai Co., Ltd., 4‐6‐10 Koishikawa, Bunkyo‐ku, Tokyo 112‐8088, Japan
Note: [] Correspondence to: Tetsuya Nakamura, Vitamin E Information and Technology Section, Eisai Co., Ltd., 4‐6‐10 Koishikawa, Bunkyo‐ku, Tokyo 112‐8088, Japan.
Abstract: Biliary and urinary metabolites were examined after intravenous administration of ^{14}C‐coenzyme Q_{10} (^{14}C‐CoQ) to guinea pigs. Cumulative recovery of administered radioactivity for up to 8 hours by bile drainage was 4.8%. The greater part of radioactivity was detected in conjugate form. After hydrolyzing with \beta ‐glucuronidase, aglycone fragments were subjected to methylation and reductive acetylation. The main metabolite was demonstrated to be Q acid‐I 1,4‐hydroquinone diacetate methyl ester (M‐1) on HPLC. Then, the main metabolite was assumed to be glucuronide of 2,3‐dimethoxy‐5‐methyl‐6‐(3'‐methyl‐5'‐carboxy‐2'‐pentenyl)‐1,4‐benzohydroquinone [Q acid‐I hydroquinone]. The cumulative urinary recovery of the administered radioactivity over 48 hours was 8.3%. The labeled samples were treated similarly to bile. The urinary metabolites of CoQ_{10} consisted of unconjugated and conjugated forms. Lyophilized urine was treated as a bile sample and analyzed. The two major metabolites were assigned to be M‐1 and Q acid‐II 1,4‐hydroquinone diacetate methyl ester (M‐2). Then, the two metabolites were assumed to be composed of Q acid‐I and 2,3‐dimethoxy‐5‐methyl‐6‐(3'‐carboxypropyl)‐1,4‐benzoquinone (Q acid‐II) in free and corresponding hydroquinone conjugate forms. To investigate the effect of exogenous labeled CoQ_{10} on unlabeled CoQ_{10} (endogenous) metabolites in urine, simultaneous quantitative determination was performed using deuterium labeled CoQ_{10} (CoQ_{10}‐d_{5}). Urine collected over a 72‐hour period after intravenous administration of CoQ_{10}‐d_{5} was processed similarly to that described above and two derivatized metabolites (M‐1 and M‐2) were quantified by gas chromatography‐mass fragmentography with the multi‐ion detection method. The analytical results showed that the addition of exogenous labeled CoQ_{10} did not influence the metabolism (or breakdown) of unlabeled (endogenous) CoQ_{10}.
