Determination of tiopronin in human plasma and study on its bioequivalence

OBJECTIVE To establish an UFLC-MS/MS method for determination ot tiopronin in human plasma and investigating the pharmacokinetics and bioequivalence of tablets and enteric-coated capsules in healthy volunteers.METHODS 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 linear range was 4.05-8 100 μg·L-1,and the limit of determination was 4.05 μg·L-1.The method recoveries were 85.0%-91.3% and the RSD of within-day and between-day was less than 15%.The main pharmacokinetic parameters of tiopronin tablets and enterosoluble capsules were as follows:Cmax(2 151.1±1 135.0) μg·L-1 and (2 363.0±1 055.1)μg·L-1;tmax(4.8±1.3) h and (4.3±1.2)h;AUC(0-t)(11 618.2±3 625.5) μg·h·L-1 and (12 824.0 ±4 464.1) μg·h·L-1;AUC(0-∞) (12 677.7±3 874.9) μg·h·L-1 and (13 803.1±4 686.0) μg·h·L-1.CONCLUSION The method is simple,sensitive and specific and the statistical analysis showed that the test and reference preparation were bioequivalent.