An LC-MS/MS method for simultaneous quantification of pyrotinib, docetaxel and paclitaxel in human plasma and its application to therapeutic drug monitoring.

Pyrotinib which is a novel irreversible tyrosine kinase inhibitor plus docetaxel or paclitaxel is effective for patients with Her2 positive early or advanced breast cancer including those who failed in first-line treatment. A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and verified for simultaneous quantification of pyrotinib, docetaxel and paclitaxel in human plasma, and applied to therapeutic drug monitoring. A reversed-phase Hypersil GOLD aQ column eluted by a gradient mobile phase composed of water and acetonitrile both containing 0.1 % formic acid under flow rate of 0.3 mL min was used for chromatographic separation. The mass spectrometry was operated in positive electrospray ionization mode, and selective reaction monitoring was applied for quantitative analysis. With imatinib as internal standard, one-step deproteinization approach with acetonitrile was applied to extract analytes and purify specimens. This method was adequately validated according to guidelines in terms of specificity and selectivity, sensitivity, linearity, extraction recovery, matrix effect, precision and accuracy, dilution integration and stability. The validated method was applied to therapeutic drug monitoring for breast cancer patients receiving pyrotinib and taxanes based chemotherapy. The therapeutic drug monitoring results showed that the plasma concentration of pyrotinib, docetaxel and paclitaxel varied significantly among individuals. Therapeutic drug monitoring for pyrotinib, docetaxel and paclitaxel is essential for individualized treatment to ensure efficacy and safety.