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Monitoring of imatinib targeted delivery in human leukocytes
Kralj, Eva (Author), Žakelj, Simon (Author), Trontelj, Jurij (Author), Pajič, Tadej (Author), Preložnik-Zupan, Irena (Author), Černelč, Peter (Author), Ostanek, Barbara (Author), Marc, Janja (Author), Kristl, Albin (Author)

URLURL - Presentation file, Visit http://www.sciencedirect.com/science/article/pii/S0928098713001693 This link opens in a new window

Abstract
The success of imatinib therapy in chronic myeloid leukemia is highly influenced by its active transport into target cells. However, the methodology for analytical evaluation of intracellular drug concentration is rare and usually reliant upon the use of radioactively labeled drugs. More specifically, there is no published method available in the literature for the determination of imatinib concentration in granulocytes. To gain further insight into the intracellular drug uptake a very reliable two-stage sample concentration procedure was devised and coupled with a sensitive ultra-high performance liquid chromatography tandem mass spectrometry. The reliability of this sample preparation and sensitivity of the analysis was confirmed by a successful validation of all necessary method parameters to an impressive lower limit of quantification of 0.5 ng imatinib per 106 cells still at the signal to noise ratio of 670. The usefulness of the method is further improved with only 6 mL of blood being necessary for patient analysis. The method has been applied to blood samples of 13 CML patients treated with imatinib and all the measured intracellular drug concentrations were within the validated range. These and further measurements will enable the research of factors which may, besides blood plasma concentration, influence the individual's response to imatinib therapy. Furthermore, individualisation of dosing based on the directly measured targeted drug delivery could be possible.

Language:English
Keywords:imatinib, kronična levkemija, granulociti, zdravljenje
Work type:Not categorized (r6)
Tipology:1.08 - Published Scientific Conference Contribution
Organization:FFA - Faculty of Pharmacy
Year:2013
Number of pages:str. 123-129
Numbering:Vol. 50, issue 1
UDC:615.2+616.15
ISSN on article:0928-0987
DOI:10.1016/j.ejps.2013.04.026 Link is opened in a new window
COBISS.SI-ID:3441521 Link is opened in a new window
Views:448
Downloads:101
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Record is a part of a proceedings

Title:Emerging Nanopharmaceuticals for Non-parenteral Application Routes
COBISS.SI-ID:3497073 This link opens in a new window

Record is a part of a journal

Title:European Journal of Pharmaceutical Sciences
Shortened title:Eur. j. pharm. sci.
Publisher:Elsevier
ISSN:0928-0987
COBISS.SI-ID:17553413 This link opens in a new window

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