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.
Subject(s)
Antineoplastic Agents/analysis , Carcinoma, Renal Cell/blood , Drug Evaluation, Preclinical/methods , Glioblastoma/drug therapy , Kidney Neoplasms/blood , Protein Kinase Inhibitors/analysis , Sunitinib/analysis , Administration, Oral , Adult , Antineoplastic Agents/blood , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Cell Line, Tumor , Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/methods , Drug Repositioning , Healthy Volunteers , Humans , Kidney Neoplasms/drug therapy , Protein Kinase Inhibitors/blood , Protein Kinase Inhibitors/therapeutic use , Sunitinib/blood , Sunitinib/therapeutic use , Tandem Mass Spectrometry/instrumentation , Tandem Mass Spectrometry/methodsABSTRACT
Hemoglobin-based oxygen carriers (HBOCs) are blood substitutes based on hemoglobin of either bovine or human origin and they can potentially be misused in elite sports to improve endurance performance. Recently, three methods have been proposed in doping control analysis to allow HBOCs screening and identification by application of electrophoresis, size-exclusion chromatography coupled with HPLC and LC coupled with tandem mass spectrometry (LC/MSMS). In view of the Athens 2004 Olympic Games, modifications were introduced in order to increase the specificity of these methods. The sample preparation protocols of the electrophoretic and SEC-HPLC methods were modified with the introduction of sequential ultra filtration steps to remove all heme containing material below 100 kDa, thus leaving only HBOCs material for analysis. Furthermore, a modification of the LC/MSMS methodology was introduced to allow full scan MS-MS spectra of peptide segments arising from the tryptic digestion of bovine HBOCs. These relatively simple methodological modifications have major impact, as far as time and cost effectiveness is concerned in doping control procedures, because they provide a useful tool in order to identify which suspect samples from the initial visual screening are due to hemolysis and exclude them from further analysis.
Subject(s)
Blood Substitutes/metabolism , Hemoglobins/metabolism , Oxygen/metabolism , Spectrometry, Mass, Electrospray Ionization/methods , Blood Substitutes/analysis , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Hemoglobins/analysis , Humans , Oxygen/analysis , Respiratory TransportABSTRACT
A study of the metabolism of isometheptene, an antispasmodic drug, in man and comparison with heptaminol metabolism, is presented in this paper. Isometheptene and two metabolites were detected in human urine after oral administration of a tablet containing isometheptene mucate. The urine level of the parent drug, which is excreted during the first 24 h, was determined using gas chromatography-mass spectrometry, after alkaline extraction with organic solvent. A minor metabolite of isometheptene was converted to heptaminol in vitro under the acidic hydrolysis conditions used for the screening procedure of stimulants and narcotics in doping control analysis.
