Simultaneous determination of paclitaxel and dasatinib in rat plasma and pharmacokinetic study on liquid chromatography‐tandem mass spectrometry

Abstract

AbstractFor most cancers, drugs in combination with chemotherapy is a promising way. Dasatinib in combination with paclitaxel can potentially be used to overcome triple‐negative breast cancer. In this work, we established an liquid chromatography‐tandem mass spectrometry method for the simultaneous determination of dasatinib and paclitaxel. Tert‐Butyl methyl ether was used to extract paclitaxel, dasatinib, and docetaxel (Internal standard). The study used multiple reaction monitoring mode with electrospray ionization . Monitoring ion pairs for paclitaxel and dasatinib was m/z 876.2→308.2 and m/z 488.3→401.1, respectively. The chromatographic separation was performed on a Hedera ODS‐2 column (150 × 2.1 mm, 5 μm; Hanbon Science and Technology, China) maintained at 40°C. The mobile phase was acetonitrile containing 0.3% formic acid (B) and water (A). The gradient elution procedure was used: 0–1 min, 70% B; 1.1–4 min, 90% B; 4.1–7 min, 70% B. The results satisfied the requirements of biological sample determination. The liquid chromatography‐tandem mass spectrometry method was successfully applied to the pharmacokinetic study of rats. The rats were simultaneously injected with dasatinib and paclitaxel by tail vein. What is more, this presented method could provide technical support for the clinical combination of these two drugs.