Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7626199 | Journal of Pharmaceutical and Biomedical Analysis | 2018 | 30 Pages |
Abstract
A new method for the quantitative analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of five tyrosine kinase inhibitors (afatinib, crizotinib, osimertinib, erlotinib and nintedanib) used in the treatment of non-small cell lung cancer (NSCLC) was developed and validated in human plasma. Separation was performed on an Accucore® C18 (2.1â¯Ãâ¯50â¯mm; 2.6â¯Î¼m) column using a gradient elution of water acidified with 0.1% (v/v) formic acid (A) and acetonitrile containing 0.1% (v/v) formic acid (B) at a flow rate of 500â¯Î¼L/min. The analytes were detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer after positive ionization with heated electrospray interface. After addition of three isotopically labeled internal standards, plasma pretreatment consisted in a simple protein precipitation. This method presented satisfactory results in terms of sensitivity, specificity, precision (intra- and inter-assay coefficient of variation from 2.6% to 10.6%), accuracy (from 96.1% to 108.5%), recovery and matrix effects. The lower limit of quantification and the linearity of these five tyrosine kinases inhibitors are suitable with the expected concentrations in clinical practice. This new bioanalytical method can be used in daily clinical practice for therapeutic drug monitoring of these tyrosine kinase inhibitors in NSCLC patients.
Keywords
EGFRIQCNintedanibAfatinibLLOQDMSOLC–MS/MSALKErlotinibinternal standardCalibration standardlower limit of quantificationDimethylsulfoxideNSCLCNon-small cell lung cancerCoefficient of VariationAnaplastic lymphoma kinaseliquid chromatography coupled with tandem mass spectrometryCrizotinibinternal quality controlEpidermal growth factor receptor
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Rafael Reis, Laurence Labat, Marie Allard, Pascaline Boudou-Rouquette, Jeanne Chapron, Audrey Bellesoeur, Audrey Thomas-Schoemann, Jennifer Arrondeau, Frédérique Giraud, Jérôme Alexandre, Michel Vidal, François Goldwasser, Benoît Blanchet,