The third-generation tyrosine kinase inhibitor (TKI), osimertinib, has revolutionized the\ntreatment of patients with non-small cell lung carcinoma with epidermal growth factor receptor\n(EGFR)-activating mutation, and resistant to first- and second-generation TKIs. Osimertinib isnow also\nproposed as a first-line therapy, thus extending the scope of applications in lung oncology. Personalized\nmedicine approaches are still necessary to monitor if patients are exposed to adequate concentrations of\nosimertinib during their treatment. It would also help to understand the appearance of new resistances\nin patients after several months of dosing with osimertinib. Liquid chromatographyâ??tandem mass\nspectrometry (LCâ??MS/MS) is currently the gold standard for the quantification of drugs in plasma\nenabling pharmacokinetic analyses and patient monitoring. In the present study, we propose an\nalternative to LCâ??MS/MS methods for the rapid and sensitive quantification of osimertinib in plasma\nusing matrix-assisted laser desorption/ionization (MALDI) â??MS. The presented assay requires only\n3 min per sample for their preparation, analysis, and data extraction, and less than 3 h for quantification.\nA lower limit of quantification (LLOQ) of 5 ng/mL in plasma was retrieved. The method was fully\nvalidated, following the guidelines of the US Food and Drug Administration (FDA) and the European\nMedicines Agency (EMA) for bioanalytical method validation. The present developments prove\nthe importance to consider alternative MS assays for time-effcient quantification of small molecule\ninhibitors in plasma in the context of personalized medicine for targeted therapies.
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