Rapid and sensitive analysis of vincristine in human plasma using on-line extraction combined with liquid chromatography/tandem mass spectrometry.
A simple and rapid method has been developed and validated for the quantitation of vincristine in human plasma by liquid chromatography/tandem mass spectrometry (LC/MS/MS) with atmospheric pressure chemical ionization using on-line solid-phase extraction. The method uses vinblastine as internal standard and the sample preparation is limited just to a plasma protein precipitation step. Further sample clean-up is carried out on-line through a perfusion column preceding an analytical phenyl LC column, the latter directly connected to the mass spectrometer. Quantitation is performed in multiple reaction monitoring mode using the transitions of m/z 825.3 --> 765.3 and 811.3 --> 751.3 for vincristine and vinblastine respectively. The assay was linear (r2 > or =0.99) in a concentration range from 0.1 to 500 ng/mL. Carry-over, measured on the experimental set-up, was less than 0.04%. Recovery for vincristine and the internal standard was within 90-95%. The intra-day and inter-day assay precision ranged from 1.2% to 6.8% RSD while mean percentage deviation from nominal value ranged from 0.01% to 6.1%. The proposed assay was found suitable for pharmacokinetics investigations and clinical therapeutic drug monitoring especially in pediatric cancer patients.
Corona
Giuseppe
G
Division of Experimental and Clinical Pharmacology, National Cancer Institute and Center for Molecular Biomedicine, Aviano (PN), Italy. giuseppe.corona@cro.it
Casetta
Bruno
B
Sandron
Sara
S
Vaccher
Emanuela
E
Toffoli
Giuseppe
G
D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014750:Vincristine / Q000097:blood*
D014750:Vincristine