pf-00299804 and alectinib

Routine therapeutic drug monitoring is a promising approach for the rational use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors. The purpose of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 5 EGFR-TKIs (afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib) and 3 ALK inhibitors (alectinib, ceritinib, and crizotinib).. A 100-mL aliquot of serum was diluted with 100 μL of 1% aqueous ammonia containing internal standards and then purified using the supported liquid extraction method. LC-MS/MS was conducted in positive ionization mode, and the method was validated according to published guidelines.. Calibration curves were linear across concentration ranges examined. The intra- and interassay accuracies were 90.7%-110.7% and 94.7%-107.6%, respectively. All intra- and interassay imprecision values were ≤10.1%. The EGFR-TKIs and ALK inhibitors examined in this study, except osimertinib, which could be stored on ice for at least 5 hours, were stable at room temperature for 3 hours. For the internal standard-normalized matrix factors, the mean recovery and percent coefficient of variation values ranged between 54%-112% and 1.7%-11.7%, respectively. This method successfully determined serum concentrations of afatinib, alectinib, erlotinib, gefitinib, and osimertinib in clinical samples. Serum levels of kinase inhibitors consistently reflected those reported in previous studies.. An LC-MS/MS method suitable for the simultaneous determination of 5 EGFR-TKIs and 3 ALK inhibitors in serum was developed and validated. The newly developed method enabled the determination of 5 of 8 target drugs examined in clinical samples. However, a large number of clinical samples need to be analyzed to verify the usefulness of the method.

Topics: Acrylamides; Afatinib; Aniline Compounds; Carbazoles; Chromatography, Liquid; Crizotinib; Erlotinib Hydrochloride; Gefitinib; Humans; Lung Neoplasms; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Quinazolinones; Sulfones; Tandem Mass Spectrometry

Topics: Acrylamides; Afatinib; Aminopyridines; Anaplastic Lymphoma Kinase; Aniline Compounds; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; B7-H1 Antigen; Carbazoles; Carcinoma, Non-Small-Cell Lung; Crizotinib; ErbB Receptors; Gefitinib; Hope; Humans; Lactams; Lung; Lung Neoplasms; Piperidines; Programmed Cell Death 1 Receptor; Pyrazoles; Quinazolinones; Survival Analysis