Globally, there has been a steady upward trend in breast cancer cases and related mortality over the past few decades. Paclitaxel is a primary drug used to treat breast cancer and other solid tumors. Various analytical methods exist for determining paclitaxel in biological matrixes, but there remains a need to optimize or develop a method aimed at a better analytical signal of interest, lower reagent consumption, and/or shorter analysis time. In this context, the aim of this study was to develop and validate a rapid and sensitive UPLC-QDa/PDA method for the quantitative determination of paclitaxel in blood plasma, using docetaxel as an internal standard. The method involves a one-step extraction via protein precipitation, followed by analysis of paclitaxel by UPLC coupled with PDA and QDa detectors. The developed method was validated in accordance with the ICH M10 guidelines for the validation of bioanalytical methods. The method exhibited high linearity, with R² = 0.9891 for calibration in solvent and R² = 0.9889 for the matrix (EDTA plasma). The LOD and LLOQ were 10 ng/mL and 20 ng/mL, respectively. The precision of the method was between 1.6 and 8% RSD, and the accuracy was between 8 and 15% RSD. Minimal matrix interference was observed. The method was successfully applied to real plasma samples, in which paclitaxel concentrations ranged from 116 ng/mL to 1878 ng/mL with a mean value of 613.09 ± 588.1 ng/mL. The developed method represents a reliable, rapid, and reproducible alternative for the quantitative determination of paclitaxel in plasma following intravenous administration of the drug.
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