ABSTRACT
Objective To establish a sensitive, simple and accurate HPLC-MS/MS method to quantify glycyrrhetic acid(glycyrrhetinic acid)in mice blood, and to further study pharmacokinetic profiles of glycyrrhetic acid after oral administration of glycyrrhizin and Bu- Zhong- Yi- Qi- Wan (BY). Methods Rats were intragastric administered of glycyrrhizin(glycyrrhizic acid, 61.5 mg/kg) and BY extract(3 g/kg, with the same mole of glycyrrhizin moiety), respectively. Plasma samples were collected after administration and extracted with liquid-liquid extraction, then by separated by liquid chromatography on a C8 reversion phase chromatographic column with gradient elution. Concentration of glycyrrhetic acid was detected by the validated HPLC-MS/MS. Non-compartmental pharmacokinetic profiles were constructed using the software of Das 2.0 software(Shanghai, China), and the pharmacokinetic parameters were compared using unpaired Student’s t-test. Results This bioanalytical method was fully validated and showed good linearity(r> 0.99), wide dynamic range(5-1000 ng/ml), and favorable accuracy and precision. Compared with the glycyrrhizin pure form group, BY significantly reduced the Cmax and AUC0-t of glycyrrhetic acid by 56% and 76%, respectively. Whereas no significant differences in Tmax, T1/2 and MRT were observed between the two groups. Conclusion The constituents in the BY prescription have significantly reduced the oral bioavailability of glycyrrhetic acid in rats than those in the glycyrrhizin pure form and the results indicate that some components in the BY have an inhibition effect on the absorption process of glycyrrhizin in the gut.
ABSTRACT
Objective To establish a sensitive,simple and accurate HPLC-MS/MS method to quantify glycyrrhetic acid(glyc?yrrhetinic acid)in mice blood,and to further study pharmacokinetic profiles of glycyrrhetic acid after oral administration of glycyrrhi?zin and Bu-Zhong-Yi-Qi-Wan(BY). Methods Rats were intragastric administered of glycyrrhizin(glycyrrhizic acid,61.5 mg/kg) and BY extract(3 g/kg,with the same mole of glycyrrhizin moiety),respectively. Plasma samples were collected after administration and extracted with liquid-liquid extraction,then by separated by liquid chromatography on a C8 reversion phase chromatographic col?umn with gradient elution. Concentration of glycyrrhetic acid was detected by the validated HPLC-MS/MS. Non-compartmental pharma?cokinetic profiles were constructed using the software of Das 2.0 software(Shanghai,China),and the pharmacokinetic parameters were compared using unpaired Student′s t-test. Results This bioanalytical method was fully validated and showed good linearity(r>0.99),wide dynamic range(5-1000 ng/ml),and favorable accuracy and precision. Compared with the glycyrrhizin pure form group, BY significantly reduced the Cmax and AUC0-t of glycyrrhetic acid by 56%and 76%,respectively. Whereas no significant differences in Tmax,T1/2 and MRT were observed between the two groups. Conclusion The constituents in the BY prescription have significantly reduced the oral bioavailability of glycyrrhetic acid in rats than those in the glycyrrhizin pure form and the results indicate that some components in the BY have an inhibition effect on the absorption process of glycyrrhizin in the gut.