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 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.
Yoo
Hye Hyun
HH
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, Chungryang, Seoul 136-791, South Korea.
Son
Junghyun
J
Lee
Jaeick
J
Kim
Nam Sun
NS
Shin
Myungyoup
M
Kang
Min-Jung
MJ
Kim
Dong-Hyun
DH
D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003903:Deuterium; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D001713:Biphenyl Compounds; C434677:dimethoxy biphenyl monocarboxylate; D003903:Deuterium