Pharmacokinetic and Metabolism Study of Ginkgolide C in Rats by UPLC‐Q‐TOF‐MS and UPLC‐MS/MS

ABSTRACT Ginkgolide C (GC), a diterpene isolated from Ginkgo biloba leaves, exhibits significant cardiovascular protective activity. The comprehensive pharmacokinetics and metabolic profile of GC in vivo are unknown. In this study, a sensitive and robust LC‐MS/MS method was first developed and validated for the determination of GC in rat plasma. The procedure necessitated only 10 μL of rat plasma and involved a protein precipitation process with acetonitrile. Chromatographic separation was achieved on a Waters Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) through gradient elution with a mobile phase composed of acetonitrile and water containing 0.1% formic acid. The MS detection was conducted in negative multiple reactions monitoring mode. The method was extensively validated including specificity, sensitivity, intraday and interday accuracy and precision, dilution, carryover, and stability according to the guidelines over the concentration range of 2–5000 ng/mL. The method was subsequently applied to the pharmacokinetic study of GC in rats after intravenous and oral administration. After intravenous administration, GC showed moderate clearance (1816.86 mL/h/kg) with a terminal elimination half‐life ( t 1/2 ) of 0.95 h. The volume of distribution ( V ss ) is 1038.83 mL/kg. After oral administration at doses of 10, 20, and 40 mg/kg, GC was quickly absorbed into the plasma and reached the peak concentration at 0.5 h. The systemic exposure of GC increased with dose dependent up to 40 mg/kg with low oral bioavailability (4.91%–6.80%). In addition, a total of 14 metabolites were detected and identified in rat plasma, urine, and feces. The biotransformation pathways were tentatively identified as oxidation, dehydrogenation, hydrogenation, hydrolysis, methylation, and sulfate conjugation. The pharmacokinetics and metabolic characteristics of GC were expounded in this study, which provided a solid foundation for in‐depth development.