UPLC-Q-TOF/MS法分析岩大戟内酯B在大鼠体内的代谢产物
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篇名: UPLC-Q-TOF/MS法分析岩大戟内酯B在大鼠体内的代谢产物
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摘要: 目的:分析岩大戟内酯B在大鼠体内的代谢产物,预测其代谢途径。方法:将大鼠随机分为空白组(灌胃0.5%羧甲基纤维素钠溶液)和给药组(灌胃岩大戟内酯B,100 mg/kg),每组8只。分别收集给药后0~12、>12~24、>24~36 h的粪便,给药后0~2、>2~8、>8~12、>12~24、>24~36、>36~48 h的尿液以及给药后1、2、8、12、24、36 h的血液样品,分别以超声提取法、固相萃取法、蛋白沉淀法处理后,采用超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF/MS)联用技术和Analyst® TF 1.7.1、PeakView® 2.2等软件联合分析、鉴定各样品中的代谢产物。结果与结论:从大鼠粪便中共检测到原型药物和7个代谢产物,从尿液和血液样品中分别检测到1、2个代谢产物。岩大戟内酯B灌胃后在大鼠体内经Ⅰ相的开环、脱水、氧化、脱氧、加氢反应等途径代谢;未检测到Ⅱ相代谢产物。
ABSTRACT: OBJECTIVE: To analyze the metabolites of jolkinolide B in rats, and predict its metabolism pathway. METHODS: The rats were randomly divided into blank group (0.5% CMC-Na, ig) and administration group (jolkinolide B, ig, 100 mg/kg), with 8 rats in each group. The fecal samples were collected at >0-12, >12-24, >24-36 hours after administration; the urine samples were collected at >0-2, >2-8, >8-12, >12-24, >24-36, >36-48 hours after administration; the blood samples were collected at 1, 2, 8, 12, 24, 36 hours after administration. UPLC-Q-TOF/MS combined with Analyst® TF 1.7.1 and PeakView® 2.2 software were used to analyze and identify the metabolites in the samples after treated with ultrasonic extraction, solid phase extraction and protein precipitation. RESULTS & CONCLUSIONS: Prototype drugs and seven metabolites were detected in rat’s fecal samples, and one or two metabolites were detected in urine and blood samples, respectively. After intragastric administration, the metabolism of jolkinolide B in rats is mainly through ring opening, oxidation, dehydration, deoxygenation and hydrogenation of phase Ⅰ, but no phase Ⅱ metabolites were detected.
期刊: 2019年第30卷第20期
作者: 马天成,孙宇,马玉坤,刘雷,孙珈,郭丽娜,刘琦
AUTHORS: MA Tiancheng,SUN Yu,MA Yukun,LIU Lei,SUN Jia,GUO Lina,LIU Qi
关键字: 岩大戟内酯B;超高效液相色谱-四极杆-飞行时间质谱联用技术;代谢产物;鉴定;大鼠
KEYWORDS: Jolkinolide B; UPLC-Q-TOF/MS; Metabolites; Identification; Rats
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