Document Detail

Concurrent determination of topotecan and model permeability markers (atenolol, antipyrine, propranolol and furosemide) by reversed phase liquid chromatography: utility in Caco-2 intestinal absorption studies.
MedLine Citation:
PMID:  17936093     Owner:  NLM     Status:  MEDLINE    
A simple, sensitive, specific and high-resolution reversed-phase liquid chromatographic method utilizing ultraviolet detection has been developed and validated for simultaneous determination of topotecan and four intestinal permeability markers (atenolol, antipyrine, propranolol and furosemide) as suggested by US-FDA. Chromatography was carried out on C-18 column with mobile phase comprising water (pH 3.0) and acetonitrile gradient pumped at a flow rate of 1 ml min(-1). The validation parameters included specificity, accuracy, precision, sensitivity and stability studies. Topotecan, an anti-cancer drug widely used in metastatic carcinoma, is a P-glycoprotein substrate having oral bioavailability of 30% with large inter-patient variability. The present method was successfully applied for demonstrating P-gp mediated transport of topotecan and its inhibition using verapamil in Caco-2 cell monolayer. The method can be used in identification of novel P-gp inhibitors for topotecan and estimating the contribution of P-gp in affecting oral bioavailability of topotecan. The other applications of method include its use in validation of Caco-2 monolayer assay for getting biowaiver based on Biopharmaceutic Classification System and its extrapolation to in situ and/or in vivo studies.
Tripta Bansal; Manoj Singh; Gautam Mishra; Sushama Talegaonkar; Roop K Khar; Manu Jaggi; Rama Mukherjee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2007-11-01
Journal Detail:
Title:  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences     Volume:  859     ISSN:  1570-0232     ISO Abbreviation:  J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-12     Completed Date:  2007-12-20     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:  261-6     Citation Subset:  IM    
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
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MeSH Terms
Antipyrine / analysis
Atenolol / analysis
Caco-2 Cells
Chromatography, High Pressure Liquid / methods*
Drug Stability
Furosemide / analysis
Intestinal Absorption / physiology*
P-Glycoprotein / physiology
Propranolol / analysis
Reproducibility of Results
Sensitivity and Specificity
Topotecan / analysis*
Reg. No./Substance:
0/P-Glycoprotein; 123948-87-8/Topotecan; 29122-68-7/Atenolol; 525-66-6/Propranolol; 54-31-9/Furosemide; 60-80-0/Antipyrine

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