Study on pharmacokinetics of ursodexycholic acid in healthy volunteers by HPLC-MS/MS

Objective To establish a HPLC-MS/MS method for determination of ursodexycholic acid in healthy human plasma and study on its pharmacokinetics in healthy human.Methods Twenty male healthy vounlteers were given a single oral dose of ursodexycholic acid 500 mg.Plasma concentrations were determined by HPLC-MS-MS method.The separation was carried out using the Shimadzu VP-ODS column with the mobile phase consisted of A: acetonitrile-H2O(35∶65);B: acetonitrile.The cetirizine was taken as the internal standard.And the plasma concentrations were detected in FSI negative selected ion monitoring mode.Results The standard curve was linear in range of 40.14～1.20×104 ng·mL-1(γ=0.995).The detection limited in the plasma was 40.14 ng·mL-1.RSD of intra-day and inter-day assays were all less than 20% in low concentrations,all less than 15% in middle or high concentrations,while the relativity recovery were 90.46%,86.51% and 93.41% respectively.The pharmacokinetic parameters were as follows:Cmax was(7.18±2.40) μg·mL-1,tmax was(2.80±0.90)h,AUC0-10 was(22.72±6.08)μg·h·mL-1,AUC0-∞ was(23.80±7.60)μg·h·mL-1.Conclusion HPLC-MS/MS method is selective,sensitive and convenient,proved to be suitable for determining concentration of ursodexycholic acid in plasma as well as pharmacokinetics studies.