Determination of Imatinib in the Blood Cells of Chronic Myelogenous Leukemia Patients by Ion-Trap Mass Spectrometry

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Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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POTĚŠIL David STEJSKAL Stanislav BORSKÝ Marek ŠIMARA Pavel HAVELKOVÁ Martina RÁZGA Filip KRONTORÁD KOUTNÁ Irena DVOŘÁKOVÁ Dana MAYER Jiří RÁČIL Zdeněk ZDRÁHAL Zbyněk

Rok publikování 2014
Druh Článek v odborném periodiku
Časopis / Zdroj Analytical Letters
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://www.tandfonline.com/doi/full/10.1080/00032719.2013.860538
Doi http://dx.doi.org/10.1080/00032719.2013.860538
Obor Analytická chemie, separace
Klíčová slova Mass spectrometry; Flow cytometry; Cell isolation technique; Chronic myelogenous leukemia; Imatinib; Peripheral blood
Popis Imatinib mesylate is a standard first-line therapy for patients with chronic myelogenous leukemia. However, there is still a significant proportion of these patients who reflect sub-optimal responses or fail imatinib therapy. Knowledge of the distribution within the studied system (e.g., peripheral blood) may be of high importance for understanding the principles of drug action and possible patient resistance to treatment. Intracellular or more precisely cell-associated, imatinib concentrations in patients, were shown to be higher compared to those in plasma, but still only limited data related to the methodology aspects of cell-associated concentrations are available. Herein is presented an assessment of the cell-associated imatinib determination assay by mass spectrometry. Three approaches were evaluated to isolate cells from the peripheral blood of chronic myelogenous leukemia patients. Erythrocyte lysis was found to cause substantial leakage of cell-associated imatinib in the first step. Selected alternative procedures utilizing density gradients did not affect the cell-associated imatinib concentration significantly. Cell isolates were subjected to flow cytometry which revealed differences in the population composition of peripheral blood cell isolates among individual patients indicating that the cell isolate composition should be addressed with the cell-associated imatinib concentration. The proposed approach may be utilized for the determination of intracellular concentration of imatinib and for other drugs in which the intracellular concentration plays a key role in the therapy.
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