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Metabolite profile of sibutramine in human urine: a liquid chromatography‐electrospray ionization mass spectrometric study
Author(s) -
Link Marek,
Hakala Kati S.,
Wsól Vladimír,
Kostiainen Risto,
Ketola Raimo A.
Publication year - 2006
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1082
Subject(s) - chemistry , chromatography , metabolite , sibutramine , mass spectrometry , derivatization , glucuronidation , tandem mass spectrometry , electrospray ionization , electrospray , demethylation , liquid chromatography–mass spectrometry , chemical ionization , ionization , ion , biochemistry , organic chemistry , microsome , medicine , obesity , enzyme , gene expression , weight loss , dna methylation , gene
We present a detailed experimental approach to detection and subsequent structural characterization of unknown metabolites of sibutramine, using liquid chromatography‐mass spectrometric techniques. The full‐, precursor ion, and constant neutral loss scan modes of a triple quadrupole mass spectrometer were used for screening sibutramine metabolites in human urine. The structural assessment of unknown metabolites was based on MS n ion trap mass spectrometric analysis and comparison of MS n spectra between the standards and compounds detected. Two phase‐I (M1 and M2) and eight phase‐II (M3‐M6) metabolites of sibutramine were found in human urine. Metabolites M1 and M2, which were found as minor metabolites, originated from N‐demethylation of sibutramine. Carbamoyl glucuronides formed from metabolites M1, M2, and their hydroxylated analogs were the main metabolites of sibutramine and were characterized by tandem mass spectrometric analysis and by the chemical modification of their structure. We demonstrate the usefulness of the chemical derivatization approach for estimation of the site of glucuronidation and propose the formation of hydroxylated regioisomers of metabolites M4 and M6. Copyright © 2006 John Wiley & Sons, Ltd.