Objective: To study the metabolites and pharmacokinetics of three main pharmacodynamic components of Xiaoer Fengye Kechuanping mixture in rats. Methods: UHPLC-ESI TOF MS and ACQUITY UPLC® HSS T3(100 mm×2.1 mm, 1.8 μm) column with a 0.1% formic acid water and acetonitrile as mobile phase were used. Gradient elution was applied and the flow rate was 0.3 mL·min-1. ESI with positive and negative ions pattern was used. After intragastric administration, serum, bile, urine, and feces of rats were collected for analyzing. The metabolites were identified by analyzing the mass-to-charge ratios, retention times, and fragments of ions. Meanwhile, UHPLC-MS/MS was used in pharmacokinetic study. Gliclazide were used as internal standard. UPLC® BEH C18(50 mm×2.1 mm, 1.7 μm) column was used. The mobile phase of 0.1 % formic acid water and acetonitrile was gradient eluted and the plasma samples were precipitated with methanol. The ESI and MRM were used for quantification. The selected monitoring ions were ephedrine m/z 166.2→148.1, glycyrrhetinic acid m/z 471.2→453.2, p-coumaric acid m/z 162.9→119.1, and internal standard m/z 322→170. Xiaoer Fengye Kechuanping mixture was gavaged by 2, 5 and 10 mL·kg-1, respectively. DAS 3.1 software was used to calculate the pharmacokinetic parameters after the plasma concentrations of three components were determined. Results: 3 prototypes and 10 metabolites which have Ⅰ phase (demethylation, oxidation) metabolism and Ⅱ phase (methylation, esterification and glucuronic acid sulfate) metabolism were identified. Meanwhile, the specificity of the three components in plasma met the requirements without interference, and all linear relationships were good (r>0.995 0), the extraction recovery and matrix effect were within the requested range. The stability of different conditions met the requirements. All three components fit the two-compartment model. Conclusion: The three main efficacy components of Xiaoer Fengye Kechuanping mixture are identified by the UHPLC-ESI TOF MS. The p-coumaric acid mainly metabolizeds in Ⅱ phases. Meanwhile, the plasma concentration of three components in rats are analyzed by UHPLC-MS/MS to calculate pharmacokinetic parameters. It is found that the absorption rate of glycyrrhetinic acid is slower than that of other two components. This paper studied the processes of Xiaoer Fengye Kechuanping mixture in the body and provide theoretical basis for exploring the pharmacodynamic material basis.
YE Xiao-yin, LI Ming, YANG Jun, TANG Jie, SHI Meng-ge, ZHANG Yong, HAN Han, ZHANG Tong
. Pharmacokinetics study of three active components from Xiaoer Fengye Kechuanping mixture after oral administration in rats*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(3)
: 394
-404
.
DOI: 10.16155/j.0254-1793.2023.03.05
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