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

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

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 000μg/L,3’-p-羟基紫杉醇的线性范围为0.50～50μg/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。

A liquid chromatography-tandem mass spectrometry （LC-MS/MS） method was explored for improving the sensitivity of paclitaxel and 3＇-p-hydroxypaclitaxel in rat plasma with metal ion. Paclitaxel is easy to produce alkali metal adduct ions （Li＋ , Na＋ , K＋ ） dur- ing mass spectrometry analysis. The mass spectrometry response of [M＋ HI＋ is low and the stability of [M＋Na]＋ is poor without adding metal ions in the mobile phase. In this study, paclitaxel and hydroxylated metabolites were quantative analyzed using lithium car- bonate reagent. The linear concentration ranges of the calibration curves for paclitaxel and 3 ＇-p-hydroxypaclitaxel are 1.00--8 000 μg/L and 0.50--50 μg/L, respectively. The meth- od is sensitive, simple and rapid, which is suitable for the pharmacokinetic study of the al- bumin-bound （nab-）paclitaxel. Lithium adduct ion is stable, high mass spectrometryresponse and low collision energy, is suitable for the quantative and structural analysis of some neutral compounds.