Comparative pharmacokinetics of triterpenic acids in normal and immunosuppressed rats after oral administration of Jujubae Fructus extract by UPLC-MS/MS

The fruit of Ziziphus jujuba (Jujubae Fructus) has been used as food and crude drug for thousands of years. Although several chemical and biological studies have revealed triterpenic acid as the main bioactive constituent of Jujubae Fructus responsible for immune-regulatory activity, only few pharmacokinetic studies have been conducted. To comprehend the kinetics of triterpenic acids and promote their curative application, a sensitive and efficient ultra-performance liquid chromatography coupled with mass spectrometry method (UPLC-MS/MS) was established. UPLC-MS/MS was applied for the simultaneous determination of ceanothic acid, epiceanothic acid, pomonic acid, alphitolic acid, maslinic acid, betulinic acid, and betulonic acid in normal and immunosuppressed rat plasma samples. After sample preparation, chromatographic separation was performed on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) with acetonitrile: methanol (1:1, v/v) and 0.5% ammonium acetate in water as mobile phase. The established method was validated and found to be specific, accurate, and precise for the seven triterpenic acids, and was successfully applied for the pharmacokinetic study of rat plasma samples. The results showed that the pharmacokinetic parameters (Cmax, Tmax, AUC0-t, AUC0-∞, and CLz/F) in the plasma samples of immunosuppressed rats were significantly different from those in normal rats, and might provide an insight for the clinical usage of triterpenic acids from Jujubae Fructus.