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J Pharm Biomed Anal. 2019 Feb 5;164:690-697. doi: 10.1016/j.jpba.2018.11.030. Epub 2018 Nov 14.

Development of a validated LC-MS/MS method for the in vitro and in vivo quantitation of sunitinib in glioblastoma cells and cancer patients.

Author information

1
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece.
2
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece; Biotechnology Laboratory, Department of Biological Applications and Technology, University of Ioannina, Ioannina, 45110, Greece.
3
Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, 26504, Rio, Greece.
4
General Chemical State Laboratory, Chemical Service of Peloponnese, Western Hellas and Ionian Islands, Department of Chemical Services of Corfu, Greece.
5
Cancer Biobank Center and Department of Hematology, School of Medicine, University of Ioannina, 45110, Ioannina, Greece.
6
St Luke's Cancer Centre, Royal Surrey County Hospital, Guildford, Surrey, UK.
7
John Fulcher Neuro-Oncology Laboratory, Imperial College London, Hammersmith Hospital, London, UK.
8
Department of Pharmacy, Laboratory of Pharmacokinetics, University of Patras, Patras, Greece.
9
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece; Cancer Biobank Center and Department of Hematology, School of Medicine, University of Ioannina, 45110, Ioannina, Greece. Electronic address: agtzakos@gmail.com.

Abstract

Sunitinib is a multi-targeted tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor and is currently being investigated against other forms of malignant tumors. Recently great interest has emerged for the application of sunitinib to glioblastoma treatment. In order to have a method with broad applicability it will be of importance to have access to a method that could be applied both in human plasma and cell uptake studies. No method has been reported thus far for the estimation of sunitinib uptake in glioma cells. We therefore set out to develop a method that could be applied for quantifying sunitinib in human plasma and in cell uptake studies. The method was validated and accredited according to ISO 17025:2005 guideline in human plasma and successfully applied to cancer patient plasma. Also, the method was effectively recruited to establish a protocol for the evaluation of sunitinib accumulation into M095K glioma cells. This method could significantly contribute to developmental phases in repurposing this drug in different cancer types.

KEYWORDS:

Cellular uptake; Glioblastoma; Human plasma; Liquid chromatography; Mass spectrometry; Sunitinib

PMID:
30472587
DOI:
10.1016/j.jpba.2018.11.030
[Indexed for MEDLINE]
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