Document Detail


Determination of pazopanib (GW-786034) in mouse plasma and brain tissue by liquid chromatography-tandem mass spectrometry (LC/MS-MS).
MedLine Citation:
PMID:  22749591     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC/MS-MS) method has been developed and validated for the quantitative determination of pazopanib in mouse plasma and brain tissue homogenate. Single liquid-liquid extraction step with ethyl acetate was employed for analysis of pazopanib and the internal standard (IS); vandetanib. HPLC separation was performed on an XTerra(®) MS C18 column 50 mm × 4.6 mm, 5.0 μm. The mobile phase consisted of 70% acetonitrile and 30% water with 0.1% formic acid, pumped at a flow rate of 0.25 ml/min. Analysis time was 3.5 min per run and both the analyte and IS eluted within 1.8-2.0 min. Multiple reactions monitoring (MRM) mode was utilized to detect the compounds of interest. The mass spectrometer was operated in the positive ion mode for detection. The precursor to product ions (Q1→Q3) selected for pazopanib and internal standard during quantitative optimization were (m/z) 438.1→357.2 and 475.0→112.2 respectively. The calibration curves were linear over the range of 3.9-1000 ng/ml in both biological matrices. Lower limit of quantification (LLOQ) for mouse plasma and brain tissue was 3.9 ng/ml. The values for inter and intra day precision and accuracy were well within the ranges acceptable for analytical assessment (<15%). This method was applied to determine brain to plasma concentration ratio and relevant pharmacokinetic parameters of pazopanib after a single intravenous dose of 5 mg/kg in FVB wild type mice.
Authors:
Mukul Minocha; Varun Khurana; Ashim K Mitra
Publication Detail:
Type:  Journal Article     Date:  2012-06-15
Journal Detail:
Title:  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences     Volume:  901     ISSN:  1873-376X     ISO Abbreviation:  J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-11-09     Revised Date:  2013-07-17    
Medline Journal Info:
Nlm Unique ID:  101139554     Medline TA:  J Chromatogr B Analyt Technol Biomed Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  85-92     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
University of Missouri-Kansas City, School of Pharmacy, Division of Pharmaceutical Sciences, Kansas City, MO 64108, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Chemistry*
Chromatography, Liquid / methods*
Drug Stability
Least-Squares Analysis
Mice
Pyrimidines / analysis*,  blood,  pharmacokinetics
Reproducibility of Results
Sensitivity and Specificity
Sulfonamides / analysis*,  blood,  pharmacokinetics
Tandem Mass Spectrometry / methods*
Grant Support
ID/Acronym/Agency:
R01 AI071199/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Pyrimidines; 0/Sulfonamides; 7RN5DR86CK/pazopanib
Comments/Corrections

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