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

被引:10
作者
Chatziathanasiadou, Maria, V [1 ]
Stylos, Evgenios K. [1 ,2 ]
Giannopoulou, Efstathia [3 ]
Spyridaki, Maria-Helen [4 ]
Briasoulis, Evangelos [5 ,6 ]
Kalofonos, Haralabos P. [3 ]
Crook, Tim [7 ]
Syed, Nelofer [8 ]
Sivolapenko, Gregory B. [9 ]
Tzakos, Andreas G. [1 ,5 ,6 ]
机构
[1] Univ Ioannina, Dept Chem, Sect Organ Chem & Biochem, GR-45110 Ioannina, Greece
[2] Univ Ioannina, Dept Biol Applicat & Technol, Biotechnol Lab, GR-45110 Ioannina, Greece
[3] Univ Patras, Dept Med, Div Oncol, Clin Oncol Lab, Rion 26504, Greece
[4] Chem Serv Peloponnese, Gen Chem State Lab, Dept Chem Serv Corfu, Corfu, Greece
[5] Univ Ioannina, Sch Med, Canc Biobank Ctr, GR-45110 Ioannina, Greece
[6] Univ Ioannina, Sch Med, Dept Hematol, GR-45110 Ioannina, Greece
[7] Royal Surrey Cty Hosp, St Lukes Canc Ctr, Guildford, Surrey, England
[8] Imperial Coll London, Hammersmith Hosp, John Fulcher Neurooncol Lab, London, England
[9] Univ Patras, Dept Pharm, Lab Pharmacokinet, Patras, Greece
关键词
Sunitinib; Liquid chromatography; Mass spectrometry; Human plasma; Cellular uptake; Glioblastoma; TYROSINE KINASE INHIBITOR; HUMAN PLASMA; PHASE-I; COMBINATION; SU11248; PHARMACOKINETICS; QUANTIFICATION; RESISTANCE; METABOLITE; CHALLENGES;
D O I
10.1016/j.jpba.2018.11.030
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
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. (C) 2018 Elsevier B.V. All rights reserved.
引用
收藏
页码:690 / 697
页数:8
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