Sensitive measurement of vinorelbine in dog plasma by liquid chromatography-electrospray ionization tandem mass spectrometry utilizing transitions from double-charged precursor ions

Biomed Chromatogr. 2011 Apr;25(4):517-23. doi: 10.1002/bmc.1477.

Abstract

A sensitive high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for measuring vinorelbine was developed. A 100 µL aliquot of plasma was spiked with deuterium-labeled internal standard and subjected to solid-phase extraction using an Oasis HLB μ-elution plate. Two microliters of the extracted samples was directly injected into LC/MS/MS. Chromatographic separation was achieved on a Capcell Pak C18 UG column (2 × 75 mm) with a gradient elution of methanol (mobile phase B) against 0.05% formic acid in aqueous 10 mm ammonium formate (mobile phase A). The LC flow rate was set to 0.28 mL/min and the gradient (solvent B concentration) was processed from 40 to 90%. In mass spectrometric detection, observation of the reaction from a double-charged precursor ion [M + 2H](2+) (m/z 390) to product ion m/z 122 provided very high sensitivity. The method was validated with a lower limit of detection of 0.2 ng/mL with 0.1 mL of plasma, and the method was used to determine the plasma pharmacokinetics of vinorelbine in dogs.

MeSH terms

  • Adsorption
  • Animals
  • Area Under Curve
  • Chromatography, Liquid / methods*
  • Dogs
  • Drug Stability
  • Hydrogen-Ion Concentration
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Solid Phase Extraction
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry / methods*
  • Vinblastine / analogs & derivatives*
  • Vinblastine / blood
  • Vinblastine / pharmacokinetics
  • Vinorelbine

Substances

  • Vinblastine
  • Vinorelbine