电喷雾串联质谱法分析阿托品及其代谢物

Analysis of Atropine and Its Metabolites in Rat Feces by Electrospray Ionization Tandem Mass Spectrometry

应用液相色谱-电喷雾串联质谱(LC-MSn)法检测阿托品及其大鼠粪样中的代谢物。收集灌胃25mg/kg阿托品的大鼠粪样,以水浸泡后,用乙酸乙酯萃取,采用LC-MS及LC-MSn等方法检测原药及其代谢物。和空白粪样及阿托品相比较,依据保留时间、一级质谱和二级质谱数据,在服药后的大鼠粪样中发现9种代谢物,分别为托品、N-去甲基托品、N-去甲基脱水阿托品、脱水阿托品、N-去甲基阿托品、羟基阿托品、N-氧化阿托品、羟基甲氧基阿托品以及托品酸等。该方法快速,简便,适合于生物样品中药物代谢物的快速鉴定。

A method is described for the identification of atropine and its metabolites in rat feces by combining liquid chromatography and tandem mass spectrometry （LC-MS^n）. The feces samples were collected after single administration of 25 mg/kg atropine to rats, and soaked in water for 1 h. Then, atropine and its metabolites were extracted by ethyl acetate. The extracted 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. By comparing retention-times, full scan MS and MS2 spectra among extracts, parent drug and blank feces, metabolite structures were deduced： nortropine, tropine, tropic acid, aponoratropine, apoatropine, noratropine, hydroxyatropine, hydroxyatropine N-oxide and hydroxy-methoxyatropine. This method is rapid, convenient, and suitable for the rapid identification of drug metabolites in biologic samples.