Chemical Research in Toxicology p. 891 - 899 (1995)
Update date:2022-09-26
Topics:
Borel
Abbott
Bioactivation of the formamide N-formylamphetamine (NFA) to 1-methyl-2- phenylethyl isocyanate (MPIC) was investigated in rats by screening bile and urine for conjugates subsequent to the phase I event. NFA was administered to rats as a mixture of protio- and pentadeuteriophenyl analogues to gain insight into the carbamoylating activity of MPIC when traced by electrospray liquid chromatography/mass spectrometry (LC/MS). An LC/MS contour generated by recording the summed mass spectrum as a function of chromatographic retention time allowed four biliary metabolites to be identified from four sets of doublets, with the peak of each doublet offset by 5 amu and ca. 0.07 min. Tandem mass spectrometry experiments allowed these metabolites to be attributed structurally to the glutathione, cysteinylglycine, cysteine, and N-acetylcysteine conjugates of the isocyanate MPIC. These assignments were subsequently validated by comparison of the LC/MS properties of the metabolites to synthetic reference compounds. Only the carbamoylated N- acetylcysteine conjugate was detected in urine. The observed excretion in bile of all metabolites of the mercapturate pathway is novel for formamide metabolism. NFA can thus be added to the short list of compounds that are eliminated in this fashion. Factors envisioned as contributory to this metabolic profile in bile include hepatorenal, enterohepatic, and biliary- hepatic cycling, in addition to possible equilibrium exchange of the isocyanate from thiocarbamate conjugates to endogenous free thiols during the course of biliary transit.
View MoreDaicel Chiral Technologies (China)CO.,LTD
Contact:021-5046-0086*8
Address:Part C, FL 5, the 16th Building, No. 69, XiYa Road, WaiGaoQiao Free Trade Zone, Shanghai, 200131, P.R.China
Contact:+86-15995924277
Address:WuZhongOu suzhou new south road 89
website:http://www.josunpharma.com
Contact:+86-311-80715268 80766839
Address:No.39, Zhaiying Street, Shijaizhuang,Hebei,China
Hangzhou Zyter Biological & Chemical Technology Co., Ltd.
website:http://www.zyterpharm.com
Contact:+86-18858184290
Address:West Wenyi Road, Cangqian, Yuhang
Changzhou naidechemical Co.Ltd
Contact:+86-519-82589807
Address:NO.25,Houyang street,Jintan,Changzhou City
Doi:10.1080/10426507.2012.700351
(2013)Doi:10.1002/jlcr.3029
(2013)Doi:10.1016/S0040-4039(00)61269-8
(1992)Doi:10.1016/j.tetlet.2013.05.152
(2013)Doi:10.1016/j.tetlet.2013.06.001
(2013)Doi:10.14233/ajchem.2013.14097
(2013)