A high-throughput UHPLC-MS/MS method for the determination of eight anti-tumor drugs in plasma

Rapidly developing UHPLC-MS/MS bioassays with high throughput and quality are challenging yet desired in routine clinics. METHODS & RESULTS: A high-throughput UHPLC-MS/MS bioassay has been built for simultaneously quantifying gefitinib, ruxolitinib, dasatinib, imatinib, ibrutinib, methotrexate, cyclophosphamide and paclitaxel. After the protein precipitation with methanol, samples were separated on an Acquity BEH C₁₈ column following a gradient elution system with methanol and 2 mM ammonium acetate in water at 40 °C with a run time of 3 min (flow rate 0.4 mL/min). Mass quantification in the positive ion SRM mode was then performed with electrospray ionization. The method of specificity, linearity, accuracy, precision, matrix effects, recovery, stability, dilution integrity and carryover were all validated as per the guideline of the China Food and Drug Administration whose values met the admissible limits. Application of the bioassay to therapeutic drug monitoring revealed important variability in the studied anti-tumour drugs. CONCLUSION: This validated approach was shown to be reliable and effective in clinical management, being a valuable support in therapeutic drug monitoring and subsequent individualized dosing optimization.