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Tytuł:
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Quantification of eight hematological tyrosine kinase inhibitors in both plasma and whole blood by a validated LC-MS/MS method.
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Autorzy:
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Verougstraete N; Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
Stove V; Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Verstraete AG; Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Stove C; Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. Electronic address: .
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Źródło:
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Talanta [Talanta] 2021 May 01; Vol. 226, pp. 122140. Date of Electronic Publication: 2021 Jan 28.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Amsterdam : Elsevier
Original Publication: Oxford : Pergamon Press
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MeSH Terms:
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Protein Kinase Inhibitors*
Tandem Mass Spectrometry*
Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Dasatinib ; Imatinib Mesylate ; Reproducibility of Results
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Contributed Indexing:
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Keywords: Chronic myeloid leukemia; LC-MS/MS; Therapeutic drug monitoring (TDM); Tyrosine kinase inhibitors
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Substance Nomenclature:
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0 (Protein Kinase Inhibitors)
8A1O1M485B (Imatinib Mesylate)
RBZ1571X5H (Dasatinib)
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Entry Date(s):
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Date Created: 20210307 Date Completed: 20210514 Latest Revision: 20210514
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Update Code:
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20240104
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DOI:
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10.1016/j.talanta.2021.122140
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PMID:
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33676691
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Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) in cancer therapy offers the potential to improve treatment efficacy while minimizing toxicity. Therefore, a high-throughput, sensitive LC-MS/MS method was developed and validated, to be used for personalized treatment of hematologic malignancies. The assay allows the simultaneous quantification in plasma (EDTA and heparin) and whole blood of eight TKIs, including bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib, which are used in the treatment of chronic and acute myeloid leukemia (CML, AML) and chronic lymphocytic leukemia (CLL). The procedure involves simple protein precipitation of 50 μL of sample, a 4-min chromatographic separation by applying gradient elution on a standard reverse phase column, and tandem mass spectrometric detection. The method was successfully validated based on international guidelines in terms of calibration curves, precision (within-run CV 0.74-16.4%; between-run CV 1.65-17.8%), accuracy (within-run bias 0.07-19.8%; between-run bias 0.05 to -17.6%), carry-over (max 19.4%, for ponatinib), selectivity, matrix-effects, recovery (ranging from 61 to 128%), stability (only issues observed for ibrutinib) and dilution integrity. Furthermore, the accuracy of the method was demonstrated by analyzing external quality controls, with a maximum bias of -11.3%. Assay applicability was demonstrated by analyzing authentic plasma and whole blood samples in order to derive blood-plasma ratios and the variation thereof. The latter are important to allow possible blood-plasma conversion when envisaging possible future implementation of TDM via dried blood microsampling. The presented method can be applied in clinical practice for performing TDM of TKIs in plasma and whole blood samples.
(Copyright © 2021 Elsevier B.V. All rights reserved.)