Drug Design, Development and Therapy (Aug 2023)
The Effect of Dihydromyricetin on the Pharmacokinetics of Fluconazole in Sprague-Dawley Rat Plasma, Based on High-Performance Liquid Chromatography–Tandem Mass Spectrometry
Abstract
Hongchuan Liu,1 Huaihuai Dong,2 Liangjun Guo,3 Yongsheng Jin,2 Lihong Liu1 1Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2School of Pharmacy, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Drug and Equipment, The 72st Group Army Hospital of PLA, Huzhou, 313000, People’s Republic of ChinaCorrespondence: Yongsheng Jin, School of Pharmacy, Naval Medical University, No. 325 of Guohe Street, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21 8187 1227, Email [email protected] Lihong Liu, Department of Pharmacy, Beijing Chaoyang Hospital, Capital Medical University, No. 8 of Gongti South Street, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel/Fax +86 10 85231786, Email [email protected]: The synergistic effect of dihydromyricetin (DHM) and fluconazole (FLC) can improve the killing effect of FLC-resistant Candida albicans in vitro and in vivo. However, it is not clear whether DHM affects the pharmacokinetic characteristics of FLC.Methods: In this study, 12 Sprague–Dawley (SD) rats were randomly divided into two groups as follows: (1) an FLC group in which rats were administered FLC only (42 mg/kg orally); (2) an FLC with the combined administration of DHM group, in which rats received an equivalent FLC dose immediately following the administration of DHM (100 mg/kg). Blood samples were collected from the ocular choroid vein of rats and converted into plasma. The concentrations of FLC in the rat plasma were then determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), and the related pharmacokinetic parameters were analysed. The initial mobile phase included 0.1% acetonitrile and water with gradient elution. Multiple reaction monitoring modes of m/z 307.2→ 220.1 for FLC, and m/z 237.1→ 194.2 for carbamazepine, were utilised to conduct quantitative analysis.Results: The calibration curve of FLC in rat plasma demonstrated good linearity in the range of 0.1– 30 μg/mL (r > 0.99), and the lower limit of quantification was 0.1 μg/mL. Moreover, the intra- and inter-day precision relative standard deviation of FLC was less than 9.09% and 6.51%, respectively. There were no significant differences in the pharmacokinetic parameters between the two groups.Conclusion: The results showed that DHM administration did not significantly alter FLC pharmacokinetics in SD rat plasma.Keywords: HPLC-MS/MS, dihydromyricetin, fluconazole, pharmacokinetic
