Study on Plasma Concentration and Bioavailability of Wogonin in Beagle's Dogs / 中草药·英文版

ABSTRACT

Objective To develop an LC-MS/MS method for determining the concentration of wogonin in dog plasma and investigate the pharmacokinetics and bioavailability by different administrations of wogonin in Beagle's dogs. Methods LC-MS/MS was employed in determining the concentration of wogonin with the selected ion monitoring model after liquid-liquid extraction with ethyl acetate of dog plasma samples. The lower limit of quantification was 0.105 μg/L. Target ions were at m/z 285.0→270.0 for wogonin and 373.3→305.3 for finasteride. In a randomized, self-control, and cross-over study, six male Beagle's dogs were treated with different administration methods in three test periods. Pharmacokinetic parameters were calculated with DAS software (Ver. 2.0). Results The calibration curve was linear in the range of 0.105-107.36 μg/L for wogonin in dog plasma samples. The main pharmacokinetic parameters of ig administration (native drug of 15 mg/kg and solution preparation of 5 mg/kg) and iv route were as follows: Cmax (2.5 ± 1.1), (7.9 ± 3.3), and (6838.7 ± 1322.1) μg/L, tmax (0.7 ± 0.3) and (0.3 ± 0.2) h for the both former, AUC0-1 (7.1 ± 2.0), (21.0 ± 3.2), and (629.7 ±111.8) μg·h/L. The absolute bioavailability of native and solution of wogonin were (0.59 ± 0.35)% and (3.65 ± 2.00)%, respectively. Conclusion The validated method is convenient, sensitive, and specific, and the improvement of wogonin solubility could remarkably increase the absolute bioavailability.