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

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

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

MATERIALS AND METHODS: 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.

RESULTS: 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 t1/2 was 2.05 ± 0.52 h. However, DHM was not readily absorbed and reached Cmax 21.63 ± 3.62 ng/mL at approximately 2.67 h following the oral administration of DHM, and t1/2 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.

DISCUSSION AND CONCLUSION: 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.