Pharmacokinetic study of unbound forsythiaside in rat blood and bile by microdialysis coupled with HPLC method

Abstract: In the present study, an in vivo microdialysis sampling method coupled to HPLC was applied for the determination of unbound forsythiaside in rat blood and bile. Microdialysis probes were inserted into the jugular vein and bile duct of rats, and then blood and bile dialysates were collected at regular time intervals after intravenous administration of forsythiaside (50 mg/kg). Dialysates were directly injected into HPLC system. Forsythiaside was separated on a C₁₈ column eluted with the mobile phase of acetonitrile–water–formic acid (16:84:0.2, v/v/v) at a flow rate of 0.8 mL/min. The wavelength of the ultraviolet detector was set at 332 nm. The lowest limit of quantification was 0.2 μg/mL for forsythiaside. Excellent linearity was found to be over a concentration range of 0.2–100 μg/mL. The main pharmacokinetic parameters of unbound forsythiaside in rat blood and bile were obtained. Furthermore, the bile-to-blood distribution ratio (AUC_bile/AUC_blood) of forsythiaside was 0.32 ± 0.06. The results indicated that forsythiaside went through hepatobiliary excretion.