Deep eutectic solvent: Improve the stability of constituents in <i>Gentianae radix et</i> rhizoma ( <i>GR</i> ) extract and oral absorption in rats

Gentianae radix et rhizoma (GR) is generally applied in clinical practice for the treatment of liver disease as a traditional Chinese medicine. This research examined the effects of a Deep Eutectic Solvent (DES), composed of lactic acid and choline chloride in a 4:1 ratio, on the stability and pharmacokinetics of the chemical constituents of GR extract. The stability of four compounds, namely 6’-O-β-D-glucosylgentiopicroside, gentiopicroside, loganic acid, and swertiamarin, was assessed in GR extract dissolved in water and 15% DES (v/v). Additionally, we developed and validated a sensitive ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method for our study, capable of simultaneously quantifying 6’-O-β-D-glucosylgentiopicroside, gentiopicroside, loganic acid, and swertiamarin in rat plasma following oral administration of GR extract. The findings indicated that the stability of these components in GR extract, which was dissolved with 15% DES (v/v), was significantly improved. The devised approach was effectively utilized in the pharmacokinetic study of these four analytes from GR extract in rats. The pharmacokinetic characteristics, including C max , T 1/2 , AUC (0-T) , and AUC (0-∞) , of GR extract dissolved in 15% DES (v/v) via oral administration were superior to those dissolved in water. The results revealed that DES may enhance the absorption of components in GR extract, extend the duration and concentration of chemical components in vivo , and possibly augment the therapeutic efficacy.