A liquid chromatography-tandem mass spectrometry method was developed and validated to quantify the small-molecule inhibitors (SMIs) brigatinib, lorlatinib, pralsetinib and selpercatinib, which are used in patients with oncogenic-driven non-small cell lung cancer. Chromatographic separation was performed on a HyPURITY ® C 18 analytical column with a gradient elution using ammonium acetate in water and in methanol, both acidified with formic acid 0,1%. Detection and quantification were performed using a triple quad mass spectrometer with an electrospray ionization interface. The assay was validated over a linear range of 50-2,500 ng/ml for brigatinib, 25-1,000 ng/ml for lorlatinib, 100-10,000 ng/ml for pralsetinib and 50-5,-000 ng/ml for selpercatinib. All four SMIs were stable for at least 7 days under cool conditions (2-8 C), and at least 24 h at room temperature (15-25 C) in K2-EDTA plasma. Under freezing conditions (À20 C), all SMIs were stable for at least 30 days, except for the lowest quality control (QC LOW ) of pralsetinib. The QC LOW of pralsetinib was stable for at least 7 days at À20 C. This method provides an efficient and simple way to quantify four SMIs with a single assay in clinical practice.
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