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Quantitative method for the determination of iso-fludelone (KOS-1803) in human plasma by LC-MS/MS.
Christner, Susan M; Parise, Robert A; Levine, Erica D; Rizvi, Naiyer A; Gounder, Mrinal M; Beumer, Jan H.
Afiliación
  • Christner SM; Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
  • Parise RA; Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
  • Levine ED; Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Rizvi NA; Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Gounder MM; Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
  • Beumer JH; Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA; Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15213, USA. Electronic address: beumerj@gmail.com.
J Pharm Biomed Anal ; 100: 199-204, 2014 Nov.
Article en En | MEDLINE | ID: mdl-25168219
Epothilones are relatively new tubulin-poison anticancer drugs. Iso-fludelone (KOS-1803) is a synthetic third generation epothilone drug discovered at Memorial Sloan Kettering Cancer Center, and currently in phase I clinical trials. We report an LC-MS/MS assay for the sensitive, accurate and precise quantitation of iso-fludelone in 0.2mL of human plasma. Validation was performed according to FDA guidance. The assay comprised of KOS-1724 as the internal standard and an MTBE liquid-liquid extraction with a water wash step. Separation was achieved with an YMC-Pack ODS-AQ column and an isocratic mobile phase of 0.1% formic acid in acetonitrile and water (70:30, v/v) at 0.3mL/min for 4min. Chromatographic separation was followed by electrospray, positive-mode ionization tandem mass spectrometric detection in the multiple reaction monitoring (MRM) mode. The assay was linear from 0.1 to 300ng/mL and was accurate (-9.41 to -7.07%) and precise (1.03-13.7%) which fulfilled FDA criteria for validation. Recovery from plasma was 73.9-79.7% and ion suppression was negligible (-22.8 to -31.3%). Plasma freeze-thaw stability (99.97-105.7%), stability for 11 months at -80°C (94.93-107.9%), and stability for 6h at room temperature (94.75-105.5%) were all acceptable. This assay is currently being applied to quantitate iso-fludelone in clinical samples.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / Espectrometría de Masa por Ionización de Electrospray / Epotilonas / Moduladores de Tubulina / Espectrometría de Masas en Tándem / Antineoplásicos Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatografía Liquida / Espectrometría de Masa por Ionización de Electrospray / Epotilonas / Moduladores de Tubulina / Espectrometría de Masas en Tándem / Antineoplásicos Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido