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

• Published in: Journal of separation science 2020-06, Vol.43 (12), p.2290-2300
• Main Authors: Ren, Guanghui, Chen, Huili, Zhang, Mei, Yang, Nan, Yang, Hui, Xu, Chuanru, Li, Jiaming, Ning, Chen, Song, Zhongjin, Zhou, Shiyu, Zhang, Siliang, Wang, Xiaoqian, Lu, Yang, Li, Ning, Zhang, Yongjie, Chen, Xijing, Zhao, Di
• Format: Article
• Language: English
• Subjects: Acetonitrile; Administration, Oral; Animals; Anticancer properties; Chromatography, High Pressure Liquid; Dogs; Elution; Female; Flavones - analysis; Flavones - pharmacokinetics; flavonoids; Flavonoids - administration & dosage; Flavonoids - analysis; Flavonoids - pharmacokinetics; Glucuronides - analysis; Glucuronides - pharmacokinetics; Injections, Intravenous; Ions; Liquid chromatography; Male; Mass spectrometry; Molecular Structure; Pharmacokinetics; Pharmacology; Sodium; Sulfonic Acids - analysis; Sulfonic Acids - pharmacokinetics; Tandem Mass Spectrometry; Tissue Distribution; ultra high performance liquid chromatography
• ISSN: 1615-9306; 1615-9314
• DOI: 10.1002/jssc.201901259

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.