Document Detail


A simple and sensitive high-performance liquid chromatographic method for the determination of vinflunine and 4-O-deacetylvinflunine from human blood.
MedLine Citation:
PMID:  20926995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Vinflunine (VFL) is the first bifluorinated tubulin-targeted agent obtained through a semi synthetic process using superacidic chemistry. Pharmacologic models evidenced a high degree of activity from several cancer lines. The intravenous formulation of VFL (Javlor, Pierre Fabre Medicament, Boulogne, France) is registered for bladder cancer and is undergoing Phase III trials for nonsmall cell lung and breast cancer. To support most of the pharmacokinetic studies in humans, a sensitive high-performance liquid chromatography bioanalytical method coupled with ultraviolet detection was developed and validated for the simultaneous quantification of VFL and its active metabolite 4-O-deacetylvinflunine. The two compounds, together with 17-bromovinorelbine, used as an internal standard, were extracted from blood (1 mL) by a liquid-liquid process under basic conditions using diethyl ether. The organic phase was then back-extracted with HCl 0.1 mol/L. Analysis was performed through a cyano column and detection was set at 268 nm. Total analysis run time was less than 15 minutes. The assay was sensitive for the two compounds to at least 2 ng/mL and calibration curves were linear up to 200 ng/mL. The between-run imprecision and the mean inaccuracy were lower than 7% and 8.3%, respectively. Blood samples were stable when stored at -70°C over 24 months. The long-term reproducibility and the suitability of this analytical method were demonstrated through the analysis of about 6000 biologic samples during the clinical development of intravenous VFL. This method is adequately sensitive to monitor the blood concentrations observed at the recommended dose defined in a clinical setting.
Authors:
Grégoire Zorza; Delphine Pellerin; Valérie Fortune; Christian Puozzo
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  32     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-11     Completed Date:  2011-02-28     Revised Date:  2011-03-01    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  United States    
Other Details:
Languages:  eng     Pagination:  734-40     Citation Subset:  IM    
Affiliation:
Institut de Recherche Pierre Fabre, Oncology Pharmacokinetic Department, Toulouse, France. gregoire.zorza@pierre-fabre.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / blood*,  pharmacokinetics
Chromatography, High Pressure Liquid
Humans
Reproducibility of Results
Spectrophotometry, Ultraviolet
Vinblastine / analogs & derivatives*,  blood,  pharmacokinetics
Chemical
Reg. No./Substance:
0/4-O-deacetylvinflunine; 0/Antineoplastic Agents, Phytogenic; 162652-95-1/vinflunine; 865-21-4/Vinblastine

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


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