Document Detail


Characterization of metabolites of meisoindigo in male and female rat kidney microsomes by high-performance liquid chromatography coupled with positive electrospray ionization tandem mass spectrometry.
MedLine Citation:
PMID:  18980268     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Meisoindigo has been effectively applied for the treatment of chronic myelogenous leukemia (CML). Although the metabolic profile of meisoindigo has been studied in liver, information relevant to extrahepatic metabolism of meisoindigo is absent in kidney so far. In this study, the metabolism of meisoindigo in rat kidney microsomes was qualitatively and quantitatively investigated by liquid chromatography/tandem mass spectrometry (LC/MS/MS), in terms of metabolite identification, metabolic stability, metabolite formation and gender effect. The metabolic profiling was accomplished by integration of multiple reaction monitoring (MRM) with conventional full MS scan followed by MS/MS methodology. The major in vitro metabolites of meisoindigo in rat kidney microsomes were identified as stereoselective 3,3' double-bond reduced meisoindigo, whereas the minor metabolites were regioselective phenyl monohydroxylmeisoindigo. An LC/MS/MS method for quantification of meisoindigo in rat kidney microsomes was also developed and validated. The calculated in vitro half-life (t(1/2)) values of meisoindigo in male and female rat kidney microsomes were 107.8 +/- 17.0 min and 130.0 +/- 12.9 min, respectively. There were no statistically significant differences between different genders in the metabolic stability profiles of meisoindigo. The reductive metabolite-formation profiles of meisoindigo in male and female rat kidney microsomes were plotted semi-quantitatively as well. The information regarding in vitro renal metabolism of meisoindigo provided a better understanding of the role of the kidney in the disposition of meisoindigo.
Authors:
Meng Huang; Lip-Wee Choo; Paul C Ho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Rapid communications in mass spectrometry : RCM     Volume:  22     ISSN:  0951-4198     ISO Abbreviation:  Rapid Commun. Mass Spectrom.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-17     Completed Date:  2009-05-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8802365     Medline TA:  Rapid Commun Mass Spectrom     Country:  England    
Other Details:
Languages:  eng     Pagination:  3835-45     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, National University of Singapore, Singapore 117543, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromatography, High Pressure Liquid / methods*
Drug Stability
Female
Indoles / chemistry,  metabolism
Kidney / chemistry*
Male
Microsomes / chemistry*
Rats
Rats, Sprague-Dawley
Spectrometry, Mass, Electrospray Ionization / methods*
Tandem Mass Spectrometry / methods*
Chemical
Reg. No./Substance:
0/Indoles; 97207-47-1/N-methylisoindigotin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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