Rapid determination of cyclovirobuxined in human plasma by HPLC-MS and It’s pharmacokinetics study

[Objective] To establish a rapid and sensitive LC/MS/MS method for the analysis of cyclovirobuxineD in plasma and study the pharmacokinetics of cyclovirobuxineD in healthy volunteers. [Methods] With this validated assay the pharmacokinetics of cyclovirobuxineD was studied in 18 healthy volunteers after a single oral administration. Plasma samples containing cyclovirobuxineD and donepezil (internal standard, IS) were extracted with liquid-liquid extraction, followed by LC separation and online MS/MS using trap ionization as an interface detection. Selecterd reaction monitoring with mass transitions m/z 403-m/z 372 and m/z 380-m/z 362 were used for cyclovirobuxineD and IS. [Results] The most low limit of determing quantity of method for cyclovirobuxineD was 0.2 μg/L,the calibration curves in plasma was linear in the range of 0.2-25 μmg/L, The RSD of precision within-day and between-day over this range were less than 6.6%. After intravenous administration of cyclovirobuxineD at the doses of 2.5, 4.0, and 6.0 mL, the Cmax values for cyclovirobuxineD were estimated to be of(2.78±1.28),(4.12±1.38)and(5.09±1.23)μg/L, respectively. The AUC increased with the increasing doses for administration, and the AUC0-28 values were(18.46±7.39),(1.86±5.03)and(25.37±11.49)μg/L·h, respectively. All Tmax values were(4.00±0) h. [Conclusion] The method can be successful1y applied to determinate the concentrations of cyclovirobuxine D, and suitable for clinical pharmacokinetics research.