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

ISSN: 1875-676X (Online)
ISSN: 1573-4129 (Print)


Volume 10, 4 Issues, 2014


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Current Pharmaceutical Analysis

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

Author(s): M. Helvenstein, S. Hambye and B. Blankert

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.

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.





Keywords: Accuracy profiles, μSPE, tyrosine kinase inhibitors, UPLC, UV-VIS detection, validation.

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Article Details

Volume: 10
Issue Number: 3
First Page: 161
Last Page: 168
Page Count: 8
DOI: 10.2174/1573412910666140619210406
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