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

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...

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Published in:Rapid communications in mass spectrometry 2006-01, Vol.20 (13), p.1981-1988
Main Authors: Yoo, Hye Hyun, Son, Junghyun, Lee, Jaeick, Kim, Nam Sun, Shin, Myungyoup, Kang, Min-Jung, Kim, Dong-Hyun
Format: Article
Language:English
Subjects:
Animals
Biphenyl Compounds - administration & dosage
Biphenyl Compounds - chemistry
Biphenyl Compounds - metabolism
Biphenyl Compounds - pharmacokinetics
Chromatography, High Pressure Liquid - methods
Deuterium
Humans
In Vitro Techniques
Injections, Intravenous
Liver - drug effects
Liver - injuries
Liver - metabolism
Male
Microsomes, Liver - metabolism
Molecular Structure
Rats
Rats, Sprague-Dawley
Spectrometry, Mass, Electrospray Ionization - methods
Tandem Mass Spectrometry - methods
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Summary: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 MSn spectral analysis. Because DDB‐S has a pseudo‐symmetrical methylenedioxy biphenyl structure, regioselective deuterium‐substituted DDB‐S (d5‐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.
ISSN:0951-4198
1097-0231
DOI:10.1002/rcm.2549