Pharmacokinetic Study of Ginkgolide B in Dog After Intravenous Administration

Abstract

Ginkgolide B (GB) is the main active ginkgolide in Ginkgo biloba leaves extract. Pharmacological study suggested that GB exhibits protective effect on nervous system impaired and can be used in the treatment of dementia, cerebral insufficiency or related cognitive decline. However, the information on pharmacokinetics of GB in vivo was limited. In this study, a sensitive LC–MS/MS analytical method was developed to accurately determinate the concentration of GB in dog plasma and applied to the pharmacokinetic study of GB in dogs after bolus injection of GB. A portion of 100 μL dog plasma was pretreated by liquid–liquid extraction using 1 mL of ethyl acetate. The GB and IS were separated on a Waters ACQUITY HSS T3 column using acetonitrile and water containing 0.1% formic acid as mobile phase, at a flow rate of 0.4 mL/min. Multiple-reaction monitoring (MRM) mode was used for quantitative analysis of GB and tolbutamide (internal standard) in negative electrospray ionization. GB showed excellent linearity with correlation coefficient >  0.99 over the concentration range of 1–5000 ng/mL. The intra and interday RSD% were less than 7.4%, while the RE% ranged from −6.1% to 9.6%. The mean extraction recovery was >  83.1%. The validated method was further successfully applied to pharmacokinetic study of GB in dog plasma. Dose-proportional pharmacokinetics of GB were observed after bolus injection administration in dogs. This comprehensive study of the pharmacokinetics of GB in dogs will provide useful information for its further development in clinic.