Determination of Senegenin and Tenuifolin in Mouse Blood by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry and Their Pharmacokinetics

Abstract

An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of senegenin and tenuifolin in mouse blood was developed. The pharmacokinetics of senegenin and tenuifolin in mice after intravenous (5 mg/kg) and oral (60 mg/kg) administration were studied, and the absolute bioavailability was calculated. A CORTECS T3 column was used, with a column temperature set at 40°C. The mobile phase was acetonitrile and 0.1% formic acid. Gradient elution was adopted, using a flow rate of 0.4 mL/min and an elution time of 4 min. Quantitative analysis was performed using electrospray ionization (ESI) with multiple reaction monitoring (MRM) in negative ion mode. Institute of Cancer Research (ICR) mice were bled from the tail vein after intravenous or oral administration of senegenin and tenuifolin. A UPLC-MS/MS method was established to determine the blood concentrations of each drug in mice, and the noncompartmental model was used to fit the pharmacokinetic parameters. Senegenin and tenuifolin showed a good linear relationship (r > 0.995) within a concentration range of 5–400 ng/mL in mouse blood. The intraday precision was <12%, the interday precision was <14%, and the accuracy was 87–109%. The recovery was >88%, and the matrix effect was 87–94%. The oral bioavailability of senegenin and tenuifolin in mice was 8.7% and 4.0%, respectively. The established UPLC-MS/MS method is suitable for pharmacokinetic studies of senegenin and tenuifolin in mice.

Neuroprotective Effects and Mechanisms of Senegenin, an Effective Compound Originated From the Roots of Polygala Tenuifolia

“…It proves that senegenin has the potential to become a clinical drug. According to a recent pharmacokinetic study, the T 1/2 value of senegenin was 2.6 ± 0.6 h, which was significantly different from previous studies (Shen et al, 2022). Although the scholars explained that the experimental animals and mixed drugs of the two studies were different, it also proved that the research on senegenin was not sufficient, and the pharmacokinetic study of senegenin in humans needs further exploration.…”

Saponin components in Polygala tenuifolia as potential candidate drugs for treating dementia

“…Tenuigenin, an active ingredient in PT extract, was tested using Institute of Cancer Research (ICR) mice. The half-lives for oral and intravenous administration were recorded at 2.6 ± 0.6 h and 1.6 ± 0.4 h, respectively, with an oral bioavailability of 8.7% ( Shen et al, 2022 ). In contrast, tenuifolin has an oral and intravenous half-life of 1.1 ± 0.2 h and 0.8 ± 0.2 h, respectively, with an oral bioavailability of 4.0% ( Shen et al, 2022 ).…”

“…The half-lives for oral and intravenous administration were recorded at 2.6 ± 0.6 h and 1.6 ± 0.4 h, respectively, with an oral bioavailability of 8.7% ( Shen et al, 2022 ). In contrast, tenuifolin has an oral and intravenous half-life of 1.1 ± 0.2 h and 0.8 ± 0.2 h, respectively, with an oral bioavailability of 4.0% ( Shen et al, 2022 ). When Sprague-Dawley (SD) rats were utilized as research subjects, tenuifolin achieved peak concentrations within 24 min, with terminal elimination half-lives of 4.8 ± 1.6 h and 2.0 ± 0.3 h for oral and intravenous injections, respectively, and an oral bioavailability of 2.0% ( Wang et al, 2015 ).…”