Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study

The pharmacokinetics properties of dihydromyricetin (DHM) are still unknown.

This study investigates the pharmacokinetic characteristics of DHM using a sensitive and reliable LC-MS/MS method.

A rapid and sensitive LC-MS/MS method was developed for the determination of DHM in male Sprague-Dawley rat plasma. Twelve rats were equally randomized into two groups, including the intravenous group (2 mg/kg) and the oral group (20 mg/kg). Blood samples (250 μL) were collected at designated time points and analyzed using this method. The pharmacokinetic parameters were calculated using DAS 3.0 pharmacokinetic software.

The calibration curve was linear within the range of 0.5-200 ng/mL (r > 0.998) with the lower limit of quantification at 0.5 ng/mL. After the intravenous injection, DHM reached a maximum concentration of 165.67 ± 16.35 ng/mL, and t_1/2 was 2.05 ± 0.52 h. However, DHM was not readily absorbed and reached C_max 21.63 ± 3.62 ng/mL at approximately 2.67 h following the oral administration of DHM, and t_1/2 was 3.70 ± 0.99 h. The MRT for the intravenous group and the oral group were 2.62 ± 0.36 and 5.98 ± 0.58 h, respectively. The AUC_(0-t) for the intravenous group and the oral group were 410.73 ± 78.12 and 164.97 ± 41.76 ng·L/mL, respectively, so the absolute bioavailability of DHM was 4.02% which was poor.

The results indicated that the bioavailability was poor. Further work needs to be conducted to investigate the reason for poor bioavailability and improve this situation.