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

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

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.

Publication types

  • Validation Study

MeSH terms

  • Administration, Oral
  • Adult
  • Antineoplastic Agents / analysis*
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / blood*
  • Carcinoma, Renal Cell / drug therapy
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods
  • Drug Evaluation, Preclinical / methods*
  • Drug Repositioning
  • Glioblastoma / drug therapy*
  • Healthy Volunteers
  • Humans
  • Kidney Neoplasms / blood*
  • Kidney Neoplasms / drug therapy
  • Protein Kinase Inhibitors / analysis*
  • Protein Kinase Inhibitors / blood
  • Protein Kinase Inhibitors / therapeutic use
  • Sunitinib / analysis*
  • Sunitinib / blood
  • Sunitinib / therapeutic use
  • Tandem Mass Spectrometry / instrumentation
  • Tandem Mass Spectrometry / methods

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Sunitinib