液相色谱-串联质谱法以锂加合离子定量分析大鼠血浆中紫杉醇和羟基代谢物

为了提高大鼠血浆中紫杉醇和羟基代谢物的检测灵敏度，本工作探索了加入金属离子的液相色谱 串联质谱联用方法。紫杉醇质谱分析时，易产生碱金属 (Li⁺、Na⁺、K⁺) 加合离子。采用未添加碱金属离子的流动相分析时，[M+H]⁺质谱响应低，[M+Na]⁺稳定性差。本实验以碳酸锂作为试剂，同时定量测定大鼠血浆中紫杉醇和羟基代谢物，紫杉醇的线性范围为1.00~8 000 μg/L，3’-p-羟基紫杉醇的线性范围为0.50~50 μg/L。本方法专属性好，准确、快速，适用于注射用紫杉醇 (白蛋白结合型) 的药代动力学研究。锂加合离子稳定性好、质谱响应高、碰撞能量低，适用于一些中性化合物的定量和结构分析。

Determination of Paclitaxel and Hydroxylated Metabolites in Rat Plasma with Lithium Adduct Ion by LC-MS/MS

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.