Determination of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dogs by using UHPLC MS/MS Application in a pharmacokinetic study

Abstract

Oroxylin A, obtained from the root of Scutellaria baicalensis Georgi, is a flavonoid with antitumor and other pharmacological activities. Our previous studies showed for the first time that it is mainly metabolized to oroxylin A sodium sulfonate by sulfotransferase enzymes in beagle dogs. In this study, rapid, universal, selective, and robust ultra-high-performance liquid chromatography-tandem mass spectrometry methods were established and fully validated to quantitatively detect oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dog plasma. The quantitative analysis for oroxylin A sodium sulfonate was reported for the first time. Plasma samples were processed with acetonitrile, a universal protein precipitant. Gradient elution was performed to resolve carryover effects and to achieve separation efficiency and sufficient chromatographic retention. The linear relationships of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in plasma were in the range of 2.0-500.0, 5.0-500.0, and 1.881-940.5 ng/mL, respectively. The assay method was successfully applied to pharmacokinetic study. This is the first paper that reveals the pharmacokinetic profile of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate after single-dose intravenous and oral administration of Oroxylin A in beagle dogs.

Keywords: flavonoids; pharmacokinetics; tandem mass spectrometry; ultra high performance liquid chromatography.