Pharmacokinetic Study of F1 in Rats by LC-MS/MS / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a LC-MS/MS method for determining F1 in rat plasma and study the pharmacokinetic properties of F1. METHODS: Ten healthy SD rats were enrolled in this study. They were randomly divided into two groups and received intragastric(10 mg·kg-1) and intravenous administration(5 mg·kg-1) of F1. After receiving F1, the concentrations of F1 in plasma were determined. Blood samples(0.1 mL)were immediately collected into heparinized tubes before injection and at 0, 0.08, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, 24 h after injection. The pharmacokinetic parameters were determined by DAS2.0 software, absolute bioavailability of F1 was calculated based on AUC and dose administered. RESULTS: The main pharmacokinetic parameters after intragastric and intravenous administration of F1 were as follows: ACU0-t(27.052±10.068), (153.878±88.777)ng·h·mL-1;AUC0-∞(31.425±9.261), (179.054±116.794)ng·h·mL-1;MRT0-t(10.722±4.335), (2.398±1.344)h; MRT0-∞ (15.651±5.917), (6.925±7.013)h;t1/2(4.294±1.534), (6.052±3.633)h;ρmax(18.394±17.856), (219.079±142.207)ng·mL-1, respectively. Absolute bioavailability value was 8.79%. CONCLUSION: This method can be used to determine the content of F1 in rat plasma. The experimental results can guide the structural optimization of F1, improve the pharmacokinetics of F1 in vivo and provide experimental basis for improving bioavailability of F1.