A sensitive assay for the quantitative analysis of vinorelbine in mouse and human EDTA plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 868; no. 1; pp. 102 - 109
• Main Authors: Damen, Carola W.N., Rosing, Hilde, Tibben, Matthijs M., van Maanen, Maria J., Lagas, Jurjen S., Schinkel, Alfred H., Schellens, Jan H.M., Beijnen, Jos H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.06.2008; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Animals; Antineoplastic Agents, Phytogenic - blood; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Edetic Acid - chemistry; Fundamental and applied biological sciences. Psychology; General pharmacology; Humans; Liquid chromatography; Mass spectrometry; Medical sciences; Mice; Pharmacology. Drug treatments; Reference Standards; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - methods; Vinblastine - analogs & derivatives; Vinblastine - blood; Vinorelbine; Mass spectrometry; Liquid chromatography; Vinorelbine; Antineoplastic agent; Human; Biological fluid; Rodentia; EDTA; Electrospray; Blood plasma; Alkaloid; Vertebrata; Mammalia; Mouse; Animal; Mass spectrometry MS/MS; Chelating agent; Antimitotic; Quantitative analysis
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2008.04.046

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 C 2 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 C 18 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.