In vitro metabolism of a new H+/K+ ATPase inhibitor DBM-819 in liver microsomes using HPLC and electrospray mass spectrometry

✍ Scribed by Sung Jin Choi; Hye-Young Ji; Hee-Yong Lee; Dong Ha Lee; Hong Lim; Hye Suk Lee

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 103 KB
• Volume: 15
• Category: Article
• ISSN: 0269-3879
• DOI: 10.1002/bmc.109

✦ Synopsis

Abstract

The metabolism of 1‐(2‐methyl‐4‐methoxyphenyl)‐4‐[(3‐hydroxypropyl)amino]‐6‐methyl‐2,3‐dihydropyrrolo[3,2c]quinoline (DBM‐819), a new H^+^/K^+^ ATPase inhibitor, has been studied by HPLC with spectrometric detection and on‐line LC‐electrospray mass spectrometry. In vitro incubation of DBM‐819 with rat liver microsomes in the presence of NADPH resulted in the production of four metabolites (M1‐4), whereas DBM‐819 was oxidized to two metabolites, M2 and M4, by human liver microsomes. M2, M3 and M4 were identified as O‐demethyl‐DBM‐819, 8‐hydroxy‐DBM‐819 and N‐dehydroxypropyl‐DBM‐819, respectively, based on LC/MS/MS analysis with authentic standards. M1 was tentatively identified as 1‐(hydroxy‐2‐methyl‐4‐methoxyphenyl)‐4‐[(3‐hydroxypropyl)amino]‐6‐methyl‐2,3‐dihydropyrrolo[3,2c]quinoline. Rat liver CYP1A1/2 catalyzed the oxidation of DBM‐819 to 8‐hydroxy‐DBM‐819 and N‐dehydroxypropyl‐DBM‐819. Human CYP3A4 was a major isozyme for the formation of O‐demethyl‐DBM‐819 as well as N‐dehydroxypropyl‐DBM‐819. Copyright © 2001 John Wiley & Sons, Ltd.