title: Quantitation of ursolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry and its pharmacokinetic study.
abstract: Ursolic acid is a hydroxy pentacyclic triterpene, which proved to have sedation, anti-inflammatory, antibacterial, antiulcer and anti-cancer activities. An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method with high selectivity, sensitivity and throughput has been established and validated for quantitation of total ursolic acid in human plasma. Plasma samples were pretreated by liquid-liquid extraction with ethyl acetate and were chromatographed by an ACQUITY UPLC BEH C(8) column (100 mm×2.1 mm, I.D., 1.7 μm) using mobile phase consisting of acetonitrile and 10 mM ammonium formate (90:10, v/v) at 0.2 mL/min. The duration of chromatography analysis was 3 min. The multiple reaction monitoring (MRM) was performed at m/z 455.1→455.0 for ursolic acid and m/z 469.3→425.2 for glycyrrhetinic acid (internal standard, IS) in the negative ion mode with electrospray ionization (ESI) source. The assay showed good linearity over the range of 10-5000 ng/mL for ursolic acid in human plasma with a lower limit of quantitation of 10 ng/mL. The mean extraction recovery was 73.2±4.5% and the matrix ion suppression ranged from -11.4% to -5.6%. The intra- and inter-day precisions were less than 7.0% and 7.2%, respectively, and the accuracy was within ±2.0%. Ursolic acid was stable during the analysis and the storage period. The validated method has been successfully applied to a pharmacokinetic study after intravenous infusion of Ursolic Acid Nano-liposomes to healthy volunteers.
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xia
authors.forename: Guangli
authors.initials: G
authors.lastname: Wei
authors.forename: Duanyun
authors.initials: D
authors.lastname: Si
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016018:Least-Squares Analysis; D008081:Liposomes; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014315:Triterpenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000097245:Ursolic Acid
chemical_list: D008081:Liposomes; D014315:Triterpenes; D000097245:Ursolic Acid