Separation and Quantitation of Acetaminophen and Its Metabolites in the Bile of Mice

Abstract

After a single dose of 14C-acetaminophen [a potentially toxic analgesic] (250 mg/kg, orally) was administered to bile duct cannulated mice, 18.1 + 2.4% of the radioactivity was recovered in the bile in the first 5 h following administration. The biliary metabolites were separated and quantitated by a combination of paper and Sephadex gel G-10 column chromatography and reversed-phase high-performance liquid chromatography. The metabolites of acetaminophen identified were: glutathione (61.17 .+-. 2.94%), glucuronide (6.89 .+-. 2.04%), sulfate (13.00 .+-. 1.51%), unchanged acetaminophen (7.55 .+-. 0.39%) and unknown (11.66 .+-. 2.83%). The identification of acetaminophen glutathione in the bile represents the first time that this metabolite has been detected in biological fluid after acetaminophen administration.