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

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. Copyright © 2010 John Wiley & Sons, Ltd.