Determination of tiopronin in human serum by LC-MS/MS: Application to relative bioavailability of two domestic preparations

Objective: To develop a LC/MS/MS method for determining the concentration of tiopronin in human serum and investigating the pharmacokinetics and bioequivalence of enterosoluble capsules and tablets in Chinese healthy volunteers.Methods:2-amino-3-thiopropionic acid was added in the collecting duct before human serum was obtained.LC/MS/MS was employed to determine the concentration in the selected-ion monitoring model after the samples were precipitated with methanol.Target ions were at m/z 162.0→105.0 for tiopronin and m/z 178.0→91.1 for the internal standard.Twenty volunteers were randomly divided into two groups(test and reference) in a double cross-over design.Pharmacokinetic parameters were calculated with DAS 2.0 program.Results:The calibration curve was linear over the range of 0.078～10 μg·mL-1.The main pharmacokinetic parameters of tiopronin enterosoluble capsules and tablets were as follows:Cmax(3.977±1.944)and(4.104±1.400)μg·mL-1,Tmax(4.000±1.686)and(4.050±1.191)h,AUC0~96 h(20.407±8.479)and(21.107±8.899)μg·h·mL-1.Conclusion:The method applied to quantitate was convenient,sensitive and specific and the statistical analysis showed that the test and reference preparation were bioequivalent.