oroxylin-a-7-o-glucuronide and 5-7-dihydroxy-6-methoxy-2-phenylchromen-4-one

Topics: Administration, Oral; Ampicillin; Animals; Area Under Curve; Bile; Chromatography, Liquid; Feces; Female; Flavones; Flavonoids; Glucuronides; Half-Life; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Tetracyclines; Tissue Distribution

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.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Dogs; Female; Flavones; Flavonoids; Glucuronides; Injections, Intravenous; Male; Molecular Structure; Sulfonic Acids; Tandem Mass Spectrometry; Tissue Distribution

Targeting therapy of anti-cancer drugs has been gaining increasing attention. Cell pharmacokinetics have been used for in vitro disposition evaluation, as well as drug-drug interaction for anti-cancer drugs, revealing their fate after entering tumor. Flavonoid compound oroxylin A (OA) possesses strong anti-cancer effects especially on the liver and breast cancer. However, despite the low bioavailability, the disposition of OA and its active metabolite in the target cancer cells remained unclear. In current study, a highly sensitive and selective solid phase extraction (SPE)-UPLC-MS/MS method was developed and validated to simultaneously quantify the concentrations of OA and its major active metabolite oroxylin A 7-O-d-glucuronide (OG) in HepG2 cell lysate and multiple subcellular organelle fractions. The proposed method appeared to be suitable for the analysis with desirable linearity(R

Topics: Antineoplastic Agents; Biological Availability; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Interactions; Flavones; Flavonoids; Glucuronides; Hep G2 Cells; Humans; Mitochondria; Reproducibility of Results; Solid Phase Extraction; Subcellular Fractions; Tandem Mass Spectrometry

This study aims to identify and quantify the six major bioactive flavones of the traditional Chinese medicine Scutellariae Radix (RS), including baicalein, baicalin, wogonin, wogonoside, oroxylin A and oroxyloside in rat after oral administration of a standardized RS extract. A novel, sensitive and selective method for simultaneous determination of these six analytes in rat brain and plasma using solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC/MS/MS) was developed and fully validated. The lower limits of quantification (LLOQs) for the six RS flavones in brain tissue were 0.02nmol/g. The LLOQs in plasma were 0.005nmol/ml for B, W and OA, 0.025nmol/ml for WG and OAG, and 0.1875nmol/ml for BG. The current study provides novel evidence of the presence of all the tested RS flavones and an isoform of BG (BG', probably baicalein-6-O-glucuronide) in the rat brain after oral administration of RS extract, suggesting their ability to permeate through the blood-brain barrier. The method was also successfully applied to the pharmacokinetic study of all these analytes in plasma after oral administration of RS extract (300mg/kg) to Sprague-Dawley rats. The developed assay method provides a useful tool for both preclinical and clinical investigations on the disposition of RS flavones in brain and plasma.

Topics: Animals; Brain; Chromatography, Liquid; Flavanones; Flavones; Flavonoids; Glucosides; Glucuronides; Male; Rats; Solid Phase Extraction; Tandem Mass Spectrometry