Sensitive and specific quantification of the anticancer agent ZD1839 (Gefitinib) in plasma by on-column focusing capillary liquid chromatography-tandem mass spectrometry.
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.
Guetens
G
G
Lab of Experimental Oncology, Department of Clinical Oncology, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium. Gunther.Guetens@med.kuleuven.ac.be
Prenen
H
H
De Boeck
G
G
Van Dongen
W
W
Esmans
E
E
Lemière
F
F
van Oosterom
A T
AT
Schöffski
P
P
de Bruijn
E A
EA
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
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib