title: Sensitive and specific quantification of the anticancer agent ZD1839 (Gefitinib) in plasma by on-column focusing capillary liquid chromatography-tandem mass spectrometry.
abstract: The development of an on-column focusing gradient capillary LC method coupled to tandem mass spectrometry (quadrupole-linear ion trap) for the quantitative determination of the anticancer agent ZD1839 (Gefitinib, Iressa) in blood plasma is described. Plasma samples (0.2 ml) were extracted with methyl tert-butyl ether. The analytes of interest, ZD1839 and the internal standard [(2)H8]ZD1839 (ZD1839-d8) were eluted on a 50 mm x 1 mm, 5 microm particle size, capillary ODS Hypersil column using an aqueous ammonium acetate gradient at 40 microl/min. Mass spectrometric detection was performed by a Q-Trap tandem mass spectrometer with electrospray positive ionisation, and monitored in the multiple reaction monitoring transitions 447 >128 and 455 >136, respectively. The limit of quantification of ZD18395 was 0.1 ng/ml. The method proved to be robust, allowing quantification of ZD1839 with sufficient precision, accuracy and sensitivity.
authors.affiliation: Lab of Experimental Oncology, Department of Clinical Oncology, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium. Gunther.Guetens@med.kuleuven.ac.be
authors.forename: G
authors.initials: G
authors.lastname: Guetens
authors.forename: H
authors.initials: H
authors.lastname: Prenen
authors.forename: G
authors.initials: G
authors.lastname: De Boeck
authors.forename: W
authors.initials: W
authors.lastname: Van Dongen
authors.forename: E
authors.initials: E
authors.lastname: Esmans
authors.forename: F
authors.initials: F
authors.lastname: Lemière
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.forename: E A
authors.initials: EA
authors.lastname: de Bruijn
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D000077156:Gefitinib; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011799:Quinazolines / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib