Author/Authors :
Damen، نويسنده , , Carola W.N. and Rosing، نويسنده , , Hilde and Tibben، نويسنده , , Matthijs M. and van Maanen، نويسنده , , Maria J. and Lagas، نويسنده , , Jurjen S. and Schinkel، نويسنده , , Alfred H. and Schellens، نويسنده , , Jan H.M and Beijnen، نويسنده , , Jos H.، نويسنده ,
Abstract :
A sensitive, specific and fast high-performance liquid chromatography/tandem mass spectrometry (HPLC–MS/MS) assay for the determination of vinorelbine in mouse and human plasma is presented. A 200 μL aliquot was extracted with solid-phase extraction (SPE) using Bond-Elut C2 cartridges. Dried extracts were reconstituted in 100 μL 1 mM ammonium acetate pH 10.5–acetonitrile–methanol (21:9:70, v/v/v) containing the internal standard vintriptol (100 ng/mL) and 10 μL volumes were injected onto the HPLC system. Separation was achieved on a 50 mm × 2.0 mm i.d. Gemini C18 column using isocratic elution with 1 mM ammonium acetate pH 10.5–acetonitrile–methanol (21:9:70, v/v/v) at a flow rate of 0.4 mL/min. HPLC run time was only 5 min. Detection was performed using positive ion electrospray ionization followed by tandem mass spectrometry (ESI–MS/MS). The assay quantifies vinorelbine from 0.1 to 100 ng/mL using human plasma sample volumes of 200 μL. With this method vinorelbine can be measured in mouse plasma samples when these samples are diluted eight times in control human plasma. Calibration samples prepared in control human plasma can be used for the quantification of the drug. The lower limit of quantification in mouse plasma is 0.8 ng/mL. This assay is used to support preclinical and clinical pharmacologic studies with vinorelbine.
