Fast quantitative analysis of four tyrosine kinase inhibitors in different human plasma samples using three-way calibration-assisted liquid chromatography with diode array detection.

A simple method has been developed by combining high-performance liquid chromatography with diode array detection with the alternating trilinear decomposition method for simultaneous determination of four tyrosine kinase inhibitors in different human plasma samples. Chromatographic separation of the analytes was performed on a reversed-phase column with methanol (65%, v/v, A) and 0.1% aqueous solution of formic acid (35%, v/v, B). Analysis time was 5.0 min per run and analytes could be completely eluted within 2.8--3.8 min. The calibration concentration ranges of vandetanib, pazopanib, afatinib and dasatinib were designed as 0.50-6.10, 0.50-6.10, 0.70-7.00 and 0.70-7.00 μg·mL(-1), respectively. The intra- and inter-day RSDs ranged between 0.1 and 8.9%. Quantitative information could be extracted from the unsegregated interferences of different human plasma samples with the aid of the "second-order advantage" of three-way (second-order) calibration methods. All results demonstrated that the proposed method for direct quantitative analysis of four tyrosine kinase inhibitors in different complex systems possessed good characteristics of rapidity, sensitivity and efficiency, and it is expected to be an attractive choice in the fast analysis of clinical samples.