The identification of in vitro metabolites of CKD-732 by liquid chromatography/tandem mass spectrometry

• Published in: Rapid communications in mass spectrometry Vol. 16; no. 21; pp. 2048 - 2053
• Main Authors: Myung, Seung-Woon, Kim, Hye-Young, Min, Hye-Ki, Kim, Dong-Hyun, Kim, Myungsoo, Cho, Hyun-Woo, Lee, Ho Sup, Kim, Joon-Kyum, Hong, Chung II
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2002
• Subjects: Animals; Anti-Bacterial Agents - analysis; Anti-Bacterial Agents - metabolism; Chromatography, High Pressure Liquid - methods; Cyclohexanes; Fatty Acids, Unsaturated - analysis; Fatty Acids, Unsaturated - metabolism; Microsomes, Liver - metabolism; Rats; Sesquiterpenes; Spectrometry, Mass, Electrospray Ionization - methods
• ISSN: 0951-4198; 1097-0231
• DOI: 10.1002/rcm.830

The structural elucidation of fourteen metabolites of CKD‐732, formed in vitro with rat liver microsomes, was performed using high‐performance liquid chromatography/electrospray ionization‐tandem mass spectrometry (HPLC/ESI‐MS/MS). To identify proposed structures of the metabolites, the product ion mass spectra of the protonated molecules ([M + H]+), the retention times on reversed‐phase HPLC, and UV‐Vis spectra were utilized. Characteristic product ions for the identification of CKD‐732 metabolites were observed at m/z 231, 236, and 252. The fragment ions at m/z 236 and 252 indicated the unchanged form and the N‐oxide of the dimethylaminoethoxycinnamoyl group, respectively. The ion at m/z 231 indicated the presence of the hydroxylated form of the fumagillol group. The N‐oxide of CKD‐732, which was detected at m/z 515 and eluted later than CKD‐732 in the reversed‐phase HPLC system, was measured as a major metabolite. Three cis‐trans isomers were also found. Copyright © 2002 John Wiley & Sons, Ltd.