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 ZD 1839 (Gefitinib, tressa) 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 [H-2(8)]ZD1839 (ZD1839-d8) were eluted on a 50 mm x 1 mm, 5 mu m particle size, capillary ODS Hypersil column using an aqueous ammonium acetate gradient at 40 mu l/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 ZD 18395 was 0.1 ng/ml. The method proved to be robust, allowing quantification of ZD 1839 with sufficient precision, accuracy and sensitivity. (c) 2005 Elsevier B.V. All rights reserved.