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The metabolism and excretion of 2‐methylaminoethoxycarbonyl‐4,4′‐dimethoxy‐5,6,5′,6′‐dimethylenedioxybiphenyl‐2′‐carboxylic acid (DDB‐S) in rats and human
Author(s) -
Yoo Hye Hyun,
Son Junghyun,
Lee Jaeick,
Kim Nam Sun,
Shin Myungyoup,
Kang MinJung,
Kim DongHyun
Publication year - 2006
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2549
Subject(s) - chemistry , methylenedioxy , excretion , moiety , glucuronidation , urine , demethylation , metabolic pathway , metabolism , carboxylic acid , chromatography , stereochemistry , biochemistry , organic chemistry , microsome , enzyme , alkyl , gene expression , halogen , dna methylation , gene
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 50 mg/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 MS n 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 © 2006 John Wiley & Sons, Ltd.