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Current Pharmaceutical Analysis
ISSN (Print): 1573-4129
ISSN (Online): 1875-676X
VOLUME: 10
ISSUE: 3
DOI: 10.2174/1573412910666140619210406      Price:  $58









Determination of Three Tyrosine Kinase Inhibitors and One Active Metabolite by an Identical and Validated Ultra-performance Liquid Chromatography-DAD Method in Human Plasma

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Author(s): M. Helvenstein, S. Hambye and B. Blankert
Pages 161-168 (8)
Abstract:
Tyrosine kinase inhibitors (TKIs) are a class of targeted drugs with antiangiogenic and antitumor activities. Due to inter-individual metabolic variability, an accurate therapeutic drug monitoring (TDM) represents a key element for the patient treatment. Here a fast and easily accessible method for the quantification of 3 TKIs (with one active metabolite) in human plasma after extraction is described.

Sample pre-treatments were performed by solid phase extraction (Oasis® MCX μElution technology). Chromatographic separation was performed on a Waters Acquity UPLC® system with diode array detection (DAD) using a gradient of ammonium formate-acetonitrile on BEH C18 2.1x50 mm column.

The analytical methods were validated by using the accuracy profiles approach (β-expectation set at 95%). The methods were successfully validated for sunitinib (10 – 250 ng/mL), N-desethyl sunitinib (15 – 250 ng/mL), axitinib (15 – 250 ng/mL) and pazopanib (20 – 200 μg/mL). The first concentration levels validated were considered as limit of quantification (LOQ).

The validated method will be used in a clinical research study to determine TKI plasma levels and in this way help physicians to optimize the posology in order to achieve the best therapeutic response for their patients.

Graphical Abstract:
Keywords:
Accuracy profiles, μSPE, tyrosine kinase inhibitors, UPLC, UV-VIS detection, validation.
Affiliation:
Laboratory of Pharmaceutical Analysis, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons - UMONS, Place du Parc 20, 7000 Mons, Belgium.