title: Liquid chromatography-tandem mass spectrometry assay for the EGFR inhibitor pelitinib in plasma.
abstract: A bioanalytical liquid chromatography-tandem mass spectrometry assay for the tyrosine kinase inhibitor pelitinib was developed and validated in plasma. Acetonitrile containing the internal standard erlotinib was used to precipitate proteins. The extract was diluted with water and then directly injected onto the sub-2μm particle, bridged ethylsilica hybrid trifunctional bonded C18 column. A gradient consisting of 0.02% (v/v) formic acid in a methanol-water mixture was used. The ionization mode of the electrospray interface was positive and the analyte was detected by a triple quadrupole mass spectrometer in the selected reaction monitoring mode. The calibration range of the assay was 1-200ng/ml. The within day precision, the between day precision, and the accuracy were 3.5-7.4%, 4.5-8.6%, and 94.0-104.8%, respectively. The stability of the drug was sufficient under all relevant conditions. The validated assay was used to measure drug levels in wild-type FVB mice and pharmacokinetic parameters were assessed.
authors.affiliation: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Dino
authors.initials: D
authors.lastname: Luethi
authors.forename: Selvi
authors.initials: S
authors.lastname: Durmus
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Schinkel
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Sparidans
mesh_terms: D000634:Aminoquinolines / Q000097:blood* / Q000493:pharmacokinetics; D000814:Aniline Compounds / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D004355:Drug Stability; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry
chemical_list: D000634:Aminoquinolines; D000814:Aniline Compounds; D047428:Protein Kinase Inhibitors; C541485:EGFR protein, mouse; D066246:ErbB Receptors; C413879:EKB 569
keywords: AUC; Bioanalytical assay; EDTA; EGFR inhibitor; FVB mouse; HESI; IS; LC–MS/MS; Pelitinib; QC; SD; SRM; absorption rate constant; area under the plasma drug concentration–time curve; elimination rate constant; ethylenediaminetetraacetic acid; half-life; heated electrospray ionization; internal standard; k(A); quality control; selected reaction monitoring; standard deviation; t(1/2); λ