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口服苦丁茶提取物后,采用 UPLC/Q-TOF-MS/MS 快速分析和研究大鼠血浆中的多种潜在生物活性三萜类化合物的药代动力学。

Rapid profiling and pharmacokinetic studies of multiple potential bioactive triterpenoids in rat plasma using UPLC/Q-TOF-MS/MS after oral administration of Ilicis Rotundae Cortex extract.

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

出版信息

Fitoterapia. 2018 Sep;129:210-219. doi: 10.1016/j.fitote.2018.07.005. Epub 2018 Jul 5.

Abstract

Triterpenoids, the major bioactive ingredients of Ilicis Rotundae Cortex, contributes a significant cardiovascular protection activity. Although many studies about the total saponins have been reported, the absorption triterpenoids and pharmacokinetic behaviors were unclear. Thus, the present study aims to comprehensive elucidate the absorption triterpenoids and their pharmacokinetics in rats after oral administration the crude extract using UPLC/Q-TOF-MS/MS. A total of forty-two triterpenoids were successfully characterized from the rat plasma, and thirty-two of them were validated by the reference substances, while the others were tentatively identified based on the mass spectral fragmental patterns. Furthermore, the plasma concentrations of six absorption bioactive triterpenoids (rotundinoside C, ilexoside O, pedunculoside, rotundic acid, rotundanonic acid and ilexgenin A) were simultaneously quantified by selected reaction monitoring in negative ionization mode. All analytes exhibited good linearity with correlation coefficients values greater than 0.99 and the LLOQ ranged from 1.2 to 3.2 ng/mL, and method validation for selectivity, precision, accuracy, recovery, matrix effect and stability were reckoned acceptable. The results were successfully applied for the multiple-component pharmacokinetic study of the six bioactive triterpenoids.

摘要

三萜类化合物是八角枫科八角枫属植物的主要生物活性成分,具有显著的心血管保护活性。虽然已经有许多关于总皂苷的研究报道,但三萜类化合物的吸收和药代动力学行为仍不清楚。因此,本研究旨在采用 UPLC/Q-TOF-MS/MS 综合阐明口服粗提取物后三萜类化合物在大鼠体内的吸收和药代动力学。从大鼠血浆中成功鉴定出 42 种三萜类化合物,其中 32 种通过对照品进行了验证,其余则根据质谱碎片模式进行了推测。此外,采用负电离模式下的选择反应监测同时定量了 6 种吸收生物活性三萜类化合物(旋覆花糖苷 C、冬青苷 O、远志糖苷、旋覆花酸、旋覆花酮酸和八角枫苷 A)的血浆浓度。所有分析物均表现出良好的线性关系,相关系数值均大于 0.99,LLOQ 范围为 1.2-3.2ng/mL,选择性、精密度、准确度、回收率、基质效应和稳定性的方法验证均符合要求。该结果成功应用于 6 种生物活性三萜类化合物的多成分药代动力学研究。

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