Liquid chromatography/quadrupole time‐of‐flight mass spectrometry in combination with online hydrogen/deuterium exchange technique for structural elucidation of phase I metabolites of iso‐phenylcyclopentylamine in rat bile. (17th March 2014)

• Record Type: Journal Article
• Authors: Liu, Xiaoxue; Wang, Suilou; Ding, Li; Chen, Xiaoping; Shen, Wenbin; Dong, Xin; Yun, Changhong; Lin, Hongda
• Is Part Of: Biomedical chromatography. Volume 28:Number 10(2014:Oct.)
• Page Start: 1335
• Page End: 1344
• Publication Date: 2014-03-17
• Subjects: Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.3170
• Languages: English
• ISSNs: 0269-3879

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>MS/MS experiment and accurate mass measurement are powerful tools in metabolite identification. However, sometimes these data do not provide enough information to assign an unambiguous structure to a metabolite. In combination with MS techniques, hydrogen/deuterium (H/D) exchange can provide additional information for structural elucidation by determination of the number of exchangeable hydrogen atoms in a structure. In this study, the principal phase I metabolites of <italic>iso</italic>‐phenylcyclopentylamine in rat bile were identified by high‐performance liquid chromatography with electrospray ionization quadrupole time‐of‐flight mass spectrometry (ESI‐Q‐TOF‐MS). Since <italic>N</italic>‐oxidation may occur because of the existence of the primary amino group in the structure, it was difficult to differentiate the hydroxylated metabolites from <italic>N</italic>‐oxides by ESI‐Q‐TOF‐MS alone. Therefore, online H/D exchange technique was applied to solve this problem. Finally, 25 phase I metabolites were detected and structurally described, in which 11 were confirmed to be <italic>N</italic>‐oxides. This study demonstrated the effectiveness of high‐resolution mass spectrometry in combination with an online H/D exchange technique in rapid identification of drug metabolites, especially in discriminating hydroxylated metabolites from <italic>N</italic>‐oxides. Copyright © 2014 John Wiley &amp; Sons, Ltd.</p> </abstract>