Background: Gynostemma pentaphyllum (Thunb.) Makino has been linked to a number of pharmacological benefits, including hepatoprotective, anti-inflammatory, antioxidative, and antihyperlipidemic activities. Gypenoside XLVI (Gyp XLVI) was a significant triterpenoid saponin reported from a sweet-taste varietas G. pentaphyllum, which has inhibitory effects and causes apoptosis on human hepatocytes and hepatoma cells. Methods: A quick, precise, and sensitive method for the quantification and pharmacokinetic research of Gyp XLVI in rats was developed utilizing UPLC-MS/MS. When extracting blood samples, protein was precipitated using methanol. An internal standard (IS) was employed, which was tolbutamide. For the chromatographic separation, a C18 column (Waters Acquity) was used with mobile phases as 0.1% formic acid and acetonitrile. Multiple reaction monitoring was used as MS detection manner with electrospray ionization in negative mode. Results: Gyp XLVI had good linearity in the 1.36‒1000.00 ng/mL concentration range. The intra- day and inter-day precisions (RSD%) and accuracy (RE%) were less than 12.7% or 8.29%, respectively. Gyp XLVI’s extraction recovery ranged from 89.5% to 104.2%. The matrix effects ranged from 75.3%‒94.3%. The outcomes of matrix interference and recovery investigations complied with the necessary variability limitations. After three hours at room temperature (25°C), 24 hours in an auto-sampler (4°C), three freeze-thaw cycles, and 30 days of storage at -20°C, the analyte in rat plasma remained stable. Gyp XLVI pharmacokinetic investigations and quantification were conducted using the validated method. The AUC0-∞ values for intravenous administration (1 mg/kg) and oral administration (10 mg/kg) were 2213.9 ± 561.5 ng·h/mL and 1032.8 ± 334.8 ng·h/mL, respectively. Gyp XLVI had a half-life (t1/2z) of 2.5 ± 0.4 h in the rats after intravenous injection and 4.2 ± 0.9 h after oral administrations. Gyp XLVI had a comparatively low oral bioavailability of 4.56%. Conclusion: This is the first time that Gyp XLVI’s pharmacokinetic properties have been investigated through various administration routes. These findings will aid in our understanding of how Gyp XLVI was metabolized in rats and how it behaved pharmacologically in vivo.

中文翻译：

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使用 UPLC-MS/MS 方法研究大鼠血浆中绞股蓝皂苷 XLVI 的药代动力学

背景：绞股蓝具有许多药理功效，包括保肝、抗炎、抗氧化和抗高血脂活性。绞股蓝皂苷 XLVI (Gyp XLVI) 是从甜味变种 G. pentaphyllum 中报道的一种重要的三萜皂苷，对人肝细胞和肝癌细胞具有抑制作用并导致细胞凋亡。方法：利用 UPLC-MS/MS 开发了一种快速、精确、灵敏的大鼠 Gyp XLVI 定量和药代动力学研究方法。提取血样时，使用甲醇沉淀蛋白质。使用内标（IS），它是甲苯磺丁脲。对于色谱分离，使用 C18 柱（Waters Acquity），流动相为 0.1% 甲酸和乙腈。 MS检测方式采用多反应监测，负电喷雾电离。结果：Gyp XLVI 在 1.36-1000.00 ng/mL 浓度范围内具有良好的线性。日内和日间精密度（RSD%）和准确度（RE%）分别小于12.7%和8.29%。 Gyp XLVI 的提取回收率为 89.5% 至 104.2%。基质效应范围为75.3%~94.3%。基质干扰和回收率研究的结果符合必要的变异性限制。在室温 (25°C) 下放置 3 小时、在自动进样器 (4°C) 中放置 24 小时、三个冻融循环以及在 -20°C 下储存 30 天后，大鼠血浆中的分析物保持稳定。使用经过验证的方法进行 Gyp XLVI 药代动力学研究和定量。静脉给药（1 mg/kg）和口服给药（10 mg/kg）的AUC0-∞值分别为2213.9±561.5 ng·h/mL和1032.8±334.8 ng·h/mL。 Gyp XLVI 在大鼠中静脉注射后的半衰期 (t1/2z) 为 2.5 ± 0.4 小时，口服给药后为 4.2 ± 0.9 小时。 Gyp XLVI 的口服生物利用度相对较低，为 4.56%。结论：这是首次通过各种给药途径研究 Gyp XLVI 的药代动力学特性。这些发现将有助于我们了解 Gyp XLVI 在大鼠体内的代谢情况及其在体内的药理学行为。