UPLC-Q-TOF/MS法分析鉴定对叶百部碱在大鼠体内的代谢产物

Identification and Analysis of Tuberostemonine Metabolites in Rats by UPLC-Q-TOF/MS

目的:分析鉴定大鼠灌胃对叶百部碱后血浆、尿液和粪便中的代谢产物,阐明对叶百部碱的代谢途径。方法:将大鼠随机分为空白组(0.3%羧甲基纤维素)与给药组(灌胃给予对叶百部碱,50 mg/kg),每组6只。分别采集大鼠灌胃给药后0.25、0.5、1、2、4、6、12 h的血浆以及给药后0~12 h、12~24 h的尿液和粪便并制备样品,采用超高效液相色谱-四级杆-飞行时间质谱法和Triple TOF^(TM)高分辨率质谱自带的软件联合分析、鉴定各样品中代谢产物的化学结构。结果:从大鼠血浆中检测到4个化合物,包括1个原型化合物和3个代谢产物,在尿液中检测到4个代谢产物,在粪便中被检测到2个代谢产物,且代谢产物主要为Ⅰ相的水合代谢产物和羟基化代谢产物,未检测到Ⅱ相代谢产物。结论:对叶百部碱灌胃后在大鼠体内主要经水合、羟基化等途径代谢。

OBJECTIVE：To analyze and identify the metabolites of tuberostemonine in rats plasma,urine and feces,and to clarify metabolic pathway of tuberostemonine. METHODS：Rats were randomly divided into blank group（0.3% carboxymethyl cellulose）and medication group（tuberostemonine 50 mg/kg,i.g.）,with 6 rats in each group. The plasma of rats was collected 0.25,0.5,1,2,4,6,12 h after intragastric administration to prepare samples. Urine and feces were collected 0-12 h and 12-24 h after administration to prepare samples. UPLC-Q-TOF/MS and software of Triple TOF^（TM）high resolution mass spectrometry were used to analyze and identifiy chemical structure of metabolites in samples. RESULTS：A total of 4 compounds were detected in rat plasma,including one prototype compound and 3 metabolites. 4 metabolites were detected in urine and 2 metabolites in feces. Phase Ⅰmetabolites of tuberostemonine mainly included hydration and hydroxylation. Phase Ⅱ metabolites were not found.CONCLUSIONS：Hydration and hydroxylation are the major metabolic transformation forms of tuberostemonine in rats in vivo.