TY - JOUR
T1 - Liquid chromatographic-mass spectrometric assay for quantitation of imatinib and its main metabolite (CGP 74588) in plasma
AU - Parise, Robert A.
AU - Ramanathan, Ramesh K.
AU - Hayes, Michael J.
AU - Egorin, Merrill J.
N1 - Funding Information:
We thank Ezekiel Woods for excellent secretarial assistance in preparation of this manuscript. We also thank Drs S. Percy Ivy, Anthony Murgo, Louise Grochow, Sandra Silberman, and Laurie Letvak for encouragement and logistical support of our effort to develop this assay. Supported, in part, by grant NCI 2P30 CA47904, grant NIH/NCRR/GCRC/#5M01RR00056, and Grant U01 CA69855.
PY - 2003/7/5
Y1 - 2003/7/5
N2 - Imatinib mesylate (Gleevec, Glivec, STI571) is a targeted, small molecule inhibitor of the oncogenes, BCR/ABL and c-KIT, and has striking antitumor activity in patients with chronic myelogenous leukemia or gastrointestinal stromal tumors. We have developed a liquid chromatographic-electrospray ionization mass spectrometric (LC-MS) method for quantifying imatinib and its main metabolite (CGP 74588) in plasma. The assay uses deuterated imatinib as the internal standard; acetonitrile deproteination; a Phenomenex Luna C18(2) (5 μm, 50×4.6 mm) reversed-phase analytical column; a gradient mobile phase of 0.1% formic acid in methanol and water; and mass spectrometric detection using electrospray positive mode electron ionization. The assay has a lower limit of quantitation (LLOQ) of 30 ng/ml and is linear between 30 and 10 000 ng/ml for both imatinib and CGP 74588. We demonstrated the suitability of this assay for imatinib using it to quantify the concentrations of imatinib and CGP 74588 in plasma of a patient given a 200-mg dose of imatinib orally. We believe that this LC-MS assay should be an important tool for future pharmacokinetic studies of imatinib.
AB - Imatinib mesylate (Gleevec, Glivec, STI571) is a targeted, small molecule inhibitor of the oncogenes, BCR/ABL and c-KIT, and has striking antitumor activity in patients with chronic myelogenous leukemia or gastrointestinal stromal tumors. We have developed a liquid chromatographic-electrospray ionization mass spectrometric (LC-MS) method for quantifying imatinib and its main metabolite (CGP 74588) in plasma. The assay uses deuterated imatinib as the internal standard; acetonitrile deproteination; a Phenomenex Luna C18(2) (5 μm, 50×4.6 mm) reversed-phase analytical column; a gradient mobile phase of 0.1% formic acid in methanol and water; and mass spectrometric detection using electrospray positive mode electron ionization. The assay has a lower limit of quantitation (LLOQ) of 30 ng/ml and is linear between 30 and 10 000 ng/ml for both imatinib and CGP 74588. We demonstrated the suitability of this assay for imatinib using it to quantify the concentrations of imatinib and CGP 74588 in plasma of a patient given a 200-mg dose of imatinib orally. We believe that this LC-MS assay should be an important tool for future pharmacokinetic studies of imatinib.
KW - CGP 74588
KW - Imatinib
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U2 - 10.1016/S1570-0232(03)00206-X
DO - 10.1016/S1570-0232(03)00206-X
M3 - Article
C2 - 12798163
AN - SCOPUS:0038359665
SN - 1570-0232
VL - 791
SP - 39
EP - 44
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
IS - 1-2
ER -