Characterizing the fragmentation of 2,5-bis (4-amidinophenyl)furan-bis-O-methylamidoxime and selected metabolites using ion trap mass spectrometry.
Characterizing the fragmentation of 2,5-bis (4-amidinophenyl)furan-bis-O-methylamidoxime and selected metabolites using ion trap mass spectrometry.
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使用离子阱质谱法表征 2,5-双 (4-脒基苯基)呋喃-双-O-甲基偕胺肟和选定代谢物的碎片。
DOI：
10.1002/rcm.676
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Tidwell,RichardR
中科院分区：
文献类型：
--
作者：
Zhou,Lian;Voyksner,RobertD;Thakker,DhirenR;Stephens,ChadE;Anbazhagan,Mariappan;Boykin,DavidW;Hall,JamesE;Tidwell,RichardR
A novel prodrug [2,5‐bis(4‐amidinophenyl)furan‐bis‐O‐methylamidoxime (DB289)] of the promising antimicrobial agent, 2,5‐bis(4‐amidinophenyl)furan (DB75), has excellent oral activity. It is currently undergoing phase II clinical evaluation as an orally administered drug candidate against African trypanosomiasis andPneumocystis cariniipneumonia. The sequential product ion (MSn) fragmentations of DB289 and selected metabolites were characterized using ion trap mass spectrometry with electrospray ionization. An unusual homolytic bond cleavage, formation of an odd‐electron ion from an even‐electron ion with the loss of a radical, was commonly seen in the fragmentation patterns of DB289 and its metabolites. BothO‐ethyl andN‐methyl homologues of DB289 were utilized to confirm this fragmentation pathway. The labile hydrogen atoms in DB289 are readily exchanged with deuterium atoms in the solvent containing deuterium oxide (D2O) instead of water. The mass shift patterns displayed in the product ion spectra of DB289 in D2O proved useful in verifying the fragmentation pathway. Octadeuterated DB289 and DB75 (d‐labeling on the diphenyl rings) showed unequivocally that the diphenylfuran moiety is not involved in the fragmentation. The fragmentation pathways uncovered in this work will facilitate structural characterization of all the metabolites produced in the metabolic activation of DB289. Copyright © 2002 John Wiley & Sons, Ltd.
