Document Detail


Simultaneous quantification of rosiglitazone and its two major metabolites, N-desmethyl and p-hydroxy rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.
MedLine Citation:
PMID:  19477697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We present a simple, rapid, and sensitive liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method for the simultaneous quantification of rosiglitazone and its two major metabolites via CYP2C8/9, N-desmethyl and p-hydroxy rosiglitazone, in human plasma. The procedure was developed and validated using rosiglitazone-d(3) as the internal standard. Plasma samples (0.1 ml) were prepared using a simple deproteinization procedure with 0.2 ml of acetonitrile containing 40 ng/ml of rosiglitazone-d(3). Chromatographic separation was carried out on a Luna C18 column (100 mm x 2.0 mm, 3-microm particle size) using an isocratic mobile phase consisting of a 60:40 (v/v) mixture of acetonitrile and 0.1% formic acid((aq)). Each sample was run at 0.2 ml/min for a total run time of 2.5 min per sample. Detection and quantification were performed using a mass spectrometer in selected reaction-monitoring mode with positive electrospray ionization at m/z 358.1-->135.1 for rosiglitazone, m/z 344.2-->121.1 for N-desmethyl rosiglitazone, m/z 374.1-->151.1 for p-hydroxy rosiglitazone, and m/z 361.1-->138.1 for rosiglitazone-d(3). The linear ranges of concentration for rosiglitazone, N-desmethyl rosiglitazone, and p-hydroxy rosiglitazone were 1-500, 1-150, and 1-25 ng/ml, respectively, with a lower limit of quantification of 1 ng/ml for all analytes. The coefficient of variation for assay precision was less than 14.4%, and the accuracy was 93.3-112.3%. No relevant cross-talk and matrix effect were observed. This method was successfully applied to a pharmacokinetic study after oral administration of a 4-mg rosiglitazone tablet to healthy male Korean volunteers.
Authors:
Kwon-Bok Kim; Dong Jun Lee; Chang-Woo Yeo; Jae-Gook Shin; Soo Kyung Bae
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2009-05-13
Journal Detail:
Title:  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences     Volume:  877     ISSN:  1873-376X     ISO Abbreviation:  J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-15     Completed Date:  2009-08-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101139554     Medline TA:  J Chromatogr B Analyt Technol Biomed Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1951-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Chromatography, Liquid / methods*
Humans
Hypoglycemic Agents / blood*,  chemistry,  pharmacokinetics
Male
Tandem Mass Spectrometry / methods*
Thiazolidinediones / blood*,  chemistry,  pharmacokinetics
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Thiazolidinediones; 122320-73-4/rosiglitazone

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


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