Quantification of the anticancer agent STI-571 in erythrocytes and plasma by measurement of sediment technology and liquid chromatography-tandem mass spectrometry

An isocratic high-performance liquid chromatographic method coupled to tandem mass spectrometry for the quantification of the revolutionary and promising anticancer agent STI-571 (tradenames Gleevec, Glivec, Imatinib) in blood plasma and red blood cells (RBCs) is described. The method involves measurement of sediment technology for RBCs and a subsequent single protein precipitation step by the addition of acetonitrile to both the RBC isolate and plasma. The sample mixture was centrifuged (10 min, 3600 g), and the supernatant filtered through a HPLC filter (0.45 mum). The analytes of interest, STI-571 and the internal standard [H-2(8)]STI-571 were eluted on a Waters Symmetry C-18 column (50x2.1 mm I.D., 3.5 mum particle size) using a methanol-0.05% ammonium acetate (72:28, v/v) mixture. STI-571 and [H-2(8)]STI-571 were detected by electrospray tandem mass spectrometry in the positive mode, and monitored in the multiple reaction monitoring transitions 494>394 and 502<394, respectively. The lower limit of quantitation of STI-571 was 2.1 ng/ml in RBCs and 1.8 ng/ml in plasma. The recovery from both plasma and RBCs was between 65 and 70%. The method proved to be robust, allowing simultaneous quantification of STI-571 in RBCs and plasma with sufficient precision, accuracy and sensitivity and is useful in monitoring the fate of this signal transduction inhibitor in whole blood of cancer patients. (C) 2003 Elsevier B.V. All rights reserved.