title: A validated assay for the quantitative analysis of vatalanib in human EDTA plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
abstract: A sensitive and accurate method for the determination of vatalanib in human EDTA plasma was developed using high-performance liquid chromatography and detection with tandem mass spectrometry. Stable isotopically labeled imatinib was used as internal standard. Plasma proteins were precipitated and an aliquot of the supernatant was directly injected onto a Phenomenex Gemini C18 analytical column (50 mm x 2.0 mm ID, 5.0 microm particle size) and then compounds were eluted with a linear gradient. The outlet of the column was connected to a Sciex API 365 triple quadrupole mass spectrometer and ions were detected in positive multiple reaction monitoring mode. The lower limit of quantification was 10 ng/mL (S/N approximately 10, CV < or = 8.4%). This method was validated over a linear range from 10 to 2500 ng/mL, and results from the validation study demonstrated a good intra- and inter-assay accuracy (inaccuracy < or = 9.57%) and precision (CV < or = 8.81%). This method has been used to determine plasma vatalanib concentrations in patients with advanced solid tumor, enrolled in a phase I pharmacokinetic trial with the drug.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. nienke.lankheet@slz.nl
authors.forename: A G
authors.initials: AG
authors.lastname: Lankheet
authors.forename: M J X
authors.initials: MJ
authors.lastname: Hillebrand
authors.forename: M H G
authors.initials: MH
authors.lastname: Langenberg
authors.forename: H
authors.initials: H
authors.lastname: Rosing
authors.forename: A D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: E E
authors.initials: EE
authors.lastname: Voest
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D015394:Molecular Structure; D010793:Phthalazines / Q000097:blood*; D011725:Pyridines / Q000097:blood*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D010793:Phthalazines; D011725:Pyridines; C404768:vatalanib