Target profiling of flavonol glycosides in the extract of Ginkgo biloba leaf and their pharmacokinetics in rat plasma by ultra-high-performance liquid chromatography with tandem mass spectrometry

The extract of Ginkgo biloba leaf is a popular herbal product or dietary supplement in the world to treat various diseases, and flavonol glycosides are considered as the main bioactive constituents. In this study, 37 flavonol glycosides were rapidly screened out by precursor ion scanning in positive ion mode with production ions at m/z 287.05, 303.05, and 317.06. Subsequently, a reliable and sensitive ultra-high-performance liquid chromatography coupledwith triple quadrupole-linear ion trap mass spectrometry approach was established and validated to quantify the 20 prototype flavonol glycosides in rat plasma. Calibration curves showed good linearity (R-2 >= 0.9894) over the corresponding concentration range. The precision, accuracy, extraction recovery, matrix effect, and stability were also satisfactory. The validated method was successfully applied to a pharmacokinetic study of prototype flavonol glycosides in rat after oral administration of the extract of G. biloba leaf. As a result, the T-max of flavonol glycosides was short at 0.11-0.60 h. Quercetin-3-O-(2",6.-di-O-rhamnosyl)-glucoside, kaempferol-3-O-(2'',6''-di-O-rhamnosyl)-glucoside, quercetin-3-O-rutinoside, quercetin- 3-O- glucosyl-(1-2)-O-rhamnoside, and kaempferol-3-O-glucoside presented relatively high systemic exposure levels with AUC(0-infinity) > 500 mu g h/L and C-max > 100 mu g/L. This study would provide the valuable information for further scientific research and clinical application of the extract of G. biloba leaf.