The metabolism and excretion of 2-methylaminoethoxycarbonyl-4,4 '-dimethoxy-5,6,5,6 '-dimethylenedioxybiphenyl-2 '-carboxylic acid (DDB-S) in rats and human

Abstract

The metabolism and excretion of 2-methylaminoethoxycarbonyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2"-carboxylic acid (DDB-S) were investigated in both rats and humans using liquid chromatography/electrospray ion trap mass spectrometry (LC/ESI-MS/MS). In rats, DDB-S was rapidly eliminated from the body after a single 50mg/kg intravenous injection, with urine being a major excretion route. DDB-S was metabolically stable; approximately 96% of the administered dose was recovered in the form of the parent compound. Nevertheless, 12 metabolites were detected in the urine and feces collected from DDB-S-treated rats. The structural characterizations of the metabolites were elucidated from the MSn spectral analysis. Because DDB-S has a pseudo-symmetrical methylenedioxy biphenyl structure, regioselective deuterium-substituted DDB-S (d(5)-DDB-S) was used to assign the metabolic modification. The major metabolic pathways of DDB-S were identified as demethylenation of the methylenedioxy moiety, O-demethylation of the methoxy moiety and glucuronidation. In addition, N-demethylation of the methylaminoethyl group was also detected as a minor reaction. Copyright (c) 2006 John Wiley & Sons, Ltd.