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Development and Validation of an UPLC-MS/MS Method for Simultaneous Determination of Fifteen Targeted Anti-Cancer Drugs in Human Plasma and Its Application in Therapeutic Drug Monitoring

In this study, an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously detect 15 targeted anti-cancer drugs: aletinib, afatinib, apatinib, icotinib, dasatinib, erlotinib, gefitinib, crizotinib, lapatinib, regorafenib, ceritinib, sorafenib, vemurafenib, imatinib, and N-desmethyl imatinib. Plasma samples were processed using a new magnetic solid phase extraction technique to extract each drug. The 15 analytes and four isotope internal standards were separated using an Agilent Eclipse XDB-C18 column (50.0 × 2.1 mm, 1.7 μm) with water containing 0.1% formic acid and acetonitrile as the mobile phase. The method verification included specificity, calibration curves, carryover, accuracy, crosstalk, precision, stability, recovery, dilution integrity, and matrix effects. The results showed that the developed UPLC-MS/MS method met the requirements of the U.S. Food and Drug Administration guidelines for methodological validation and could be used to monitor plasma concentrations. Meanwhile, we also found that the plasma concentrations of these targeted anti-cancer drugs showed large individual differences, which is not conducive to the treatment of tumors. Therefore, therapeutic drug monitoring of these 15 targeted anti-cancer drugs is necessary to improve the efficacy and reduce the side effects of cancer treatment.