液相色谱-串联质谱法鉴定大鼠血浆中的东莨菪碱及其代谢物

Identification of Scopolamine and Its Metabolites in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry

建立了鉴别东莨菪碱及其代谢物的液相色谱-电喷雾离子阱串联质谱(LC-MSn)联用方法。取单剂量灌胃50 mg/kg东莨菪碱的大鼠血样,甲醇沉淀蛋白,采用LC-MS及LC-MSn等方法分析血样。和空白血样及东莨菪碱相比较,根据血样中代谢物分子量的变化(ΔM)及其多级质谱数据,鉴定并阐述其结构。结果在服药后的大鼠血样中发现7种代谢物,分别为莨菪品、N-去甲基莨菪品、脱水东莨菪碱,N-去甲基脱水东莨菪碱、N-去甲基东莨菪碱、氧化东莨菪碱以及托品酸等。该方法灵敏,快速,简便,适合于药物及其代谢物的快速鉴定。

A method is described for the identification of scopolamine and its metabolites in rat plasma by combining liquid chromatography and tandem mass spectrometry （LC-MS^n）. Methanol was added in the plasma sampled from rats after single administration of 50 mg/kg scopolamine to precipitate protein, then, the preheated samples were separated on a reversed-phase C18 column using a mobile phase of methanol/ammonium acetate （2 mmol/L, adjusted to pH 3.5 with formic acid） （70：30, V/V） and detected by LC-MS^n. Identification of the metabolites and their structural elucidation were performed by comparing their changes in molecular masses （AM）, retention-times and full scan MS^n spectra with those of the parent drug and blank plasma. The results revealed that the parent drug and its seven metabolites （norscopine, scopine, tropic acid, aponorscopolamine, aposcopolamine, norscopolamine, hydroxyscopolamine ） existed in rat plasma. This method is sensitive, rapid, simple, and it is suitable to the rapid identification of drug and its metabolits.