Development and validation of a sensitive UHPLC-MS/MS method for the measurement of β-elemonic acid in rat plasma and tissues and its application to pharmacokinetics and tissue distribution study

Abstract

β-Elemonic acid is one of the main active ingredients isolated from Boswellia carterii Birdw. which has been reported to exhibit potential anti-inflammatory and anti-cancer activities. There is few information about pharmacokinetics and tissue distribution of β-elemonic acid by now. In this study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method has been developed and validated to determine β-elemonic acid in rat plasma and various tissues after intragastric administration. Oleanolic acid was chosen as an internal standard (IS) and the plasma/tissue samples were pretreated with one-step liquid–liquid extraction. Chromatographic separation was accomplished on Eclipse Plus C18 analytical column (2.1 × 50 mm, 1.8 μm) utilizing a gradient mobile phase system consisting of water (with 0.1% ammonia-solution) and acetonitrile. β-Elemonic acid and IS were detected and quantified using negative electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 453.3 → 423.5 for β-elemonic acid and m/z 455.3 → 407.6 for IS. β-Elemonic acid showed good linearity over the investigated concentration range (r > 0.9934) in rat plasma and tissue sample. The method was successfully applied for determination of β-elemonic acid in bio-samples. A bimodal phenomenon appeared in the plasma concentration–time curve of the β-elemonic acid. The highest tissue concentrations were found in the intestine including jejunum, ileum and colon.