Publication details

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

Authors

POTĚŠIL David STEJSKAL Stanislav BORSKÝ Marek ŠIMARA Pavel HAVELKOVÁ Martina RÁZGA Filip KRONTORÁD KOUTNÁ Irena DVOŘÁKOVÁ Dana MAYER Jiří RÁČIL Zdeněk ZDRÁHAL Zbyněk

Year of publication 2014
Type Article in Periodical
Magazine / Source Analytical Letters
MU Faculty or unit

Faculty of Medicine

Citation
Web http://www.tandfonline.com/doi/full/10.1080/00032719.2013.860538
Doi http://dx.doi.org/10.1080/00032719.2013.860538
Field Analytic chemistry
Keywords Mass spectrometry; Flow cytometry; Cell isolation technique; Chronic myelogenous leukemia; Imatinib; Peripheral blood
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info