Pharmacokinetics, bioavailability, excretion, and metabolic analysis of Schisanlactone E, a bioactive ingredient from Kadsura heteroclita (Roxb) Craib, in rats by UHPLC-MS/MS and UHPLC-Q-Orbitrap HRMS
Pharmacokinetics, bioavailability, excretion, and metabolic analysis of Schisanlactone E, a bioactive ingredient from Kadsura heteroclita (Roxb) Craib, in rats by UHPLC-MS/MS and UHPLC-Q-Orbitrap HRMS
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通过 UHPLC-MS/MS 和 UHPLC-Q-Orbitrap HRMS 对五味子内酯 E（来自南五味子 (Roxb) Craib 的生物活性成分）在大鼠体内的药代动力学、生物利用度、排泄和代谢进行分析。
DOI：
10.1016/j.jpba.2019.112875
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发表时间：
2020-01-01
影响因子：
3.4
通讯作者：
Wang, Wei
中科院分区：
文献类型：
--
作者：
Liu, Rongxia;Liu, Qianqian;Wang, Wei
五味子内酯E （Schisanlactone E， SE）是从菟丝子（Kadsura heteroclita, Roxb） crabb茎中提取的一种生物活性成分。SE具有抗肿瘤、抗白血病等多种药理活性。然而，对其吸收、分布、代谢和排泄的研究却很少。本研究为SE在大鼠体内的代谢和药代动力学研究建立了新的定性定量分析方法。建立了UHPLC-MS/MS测定大鼠血浆、尿液和粪便中硒含量的方法。样品用甲醇沉淀，在多反应监测模式下进行分析。验证了所建立的方法，并应用于口服（6 mg/kg）或静脉注射（2 mg/1kg）给药后SE的药代动力学、生物利用度和排泄分析。SE的绝对口服生物利用度约为79.3%。口服给药后48 h内SE主要通过粪便排出，排泄率为41.7%，尿中未检出SE。此外，建立了UHPLC-Q-Orbitrap HRMS方法，用于筛选大鼠血浆、尿液和粪便中的SE代谢物。代谢产物采用固相萃取法提取，全MS/dd-MS2扫描模式分析。结果，通过三步分析策略鉴定出15种代谢物，其中包括11种I期代谢物和4种II期代谢物。预测SE的羧基、五元环和六元α、β -不饱和内酯环为主要代谢位点。该研究为SE的药代动力学和代谢谱的研究提供了全面的见解，为SE和异食龙葵的进一步开发利用提供了参考。(C) 2019 Elsevier B.V.版权所有
Schisanlactone E (SE) is a bioactive ingredient extracted from the stem of Kadsura heteroclita (Roxb) Craib. SE has various pharmacological activity such as anti-tumor and anti-leukemia effects. However, its absorption, distribution, metabolism, and excretion have rarely been examined. In this study, new quali-quantitative analytical methods were developed for metabolic and pharmacokinetic studies of SE in rats. A UHPLC-MS/MS method was developed to determine SE in rat plasma, urine, and feces. Samples were precipitated with methanol and analyzed in multiple reaction monitoring mode. The established method was validated and applied to the pharmacokinetics, bioavailability, and excretion analysis of SE after oral (6 mg/kg) or intravenous (2 mg/1kg) administration. The absolute oral bioavailability of SE was approximately 79.3%. After oral administration, SE was mainly excreted via feces with a rate of 41.7% for 48 h. SE could not be detected in urine. Furthermore, a UHPLC-Q-Orbitrap HRMS method was developed for the metabolite screening of SE in rat plasma, urine, and feces. Metabolites were extracted by solid phase extraction and analyzed with full MS/dd-MS2 scan mode. As a result, 15 metabolites including 11 phase I and 4 phase II metabolites were identified by a three-step analytical strategy. The carboxyl group, the five membered ring, and the six membered alpha,beta-unsaturated lactone ring of SE could be predicted as the main metabolic sites. This study provides comprehensive insights into the pharmacokinetic and metabolic profiles of SE, and would be valuable for future development and utilization of SE and Kadsura heteroclita. (C) 2019 Elsevier B.V. All rights reserved.