Abstract: A liquid chromatography-tandemmass spectrometry (LC-MS/MS) method was explored for improving the sensitivityof paclitaxel and 3’-p-hydroxypaclitaxelin rat plasma with metal ion. Paclitaxel is easy to produce alkali metal adductions (Li⁺, Na⁺, K⁺) during mass spectrometryanalysis. The mass spectrometry response of M+H⁺ is low and thestability of M+Na⁺ is poor without adding metal ions in the mobilephase. In this study, paclitaxel and hydroxylated metabolites were quantativeanalyzed using lithium carbonate reagent. The linear concentration ranges ofthe calibration curves for paclitaxel and 3’-p-hydroxypaclitaxelare 1.00—8000 μg/L and 0.50—50 μg/L,respectively. The method is sensitive, simple and rapid, which is suitable forthe pharmacokinetic study of the albumin-bound (nab-)paclitaxel. Lithium adduction is stable, high mass spectrometry response and low collision energy, is suitable for thequantative and structural analysis of some neutral compounds.