Bioequivalence and pharmacokinetic study of trimetazidine dihydrochloride in human plasma by using LC-MS/MS

Objective: To determine trimetazidine in human plasma by LC-MS/MS method,and to investigate its pharmacokinetics and bioequivalence.Methods: A two-way crossover study was adopted and the test and reference formulations containing 20 mg trimetazidine dihydrochloride were administered to 20 healthy male volunteers,respectively.Plasma concentrations were analyzed by a validated LC-MS / MS method after precipitated by addition of 10% trichloracetic acid solution.The pharmacokinetic parameters were calculated and bioequivalence was evaluated.Results: The calibration curve was linear in the range over 0.05 ~ 200 ng·mL- 1with LLOQ of 0.05 ng·mL- 1.Absolute recovery was 89.02 ~ 93.75%.Accuracy and precision were conformed to fit the requirement.The pharmacokinetic parameters for the test and reference tablets were as follows: C max were(50.98 ± 9.65) and(50.53 ±8.98) ng·mL- 1,T max were(1.5 ± 0.4) and(1.5 ± 0.3) h,t 1 /2 were(5.89 ± 0.47) and(5.77 ± 0.56) h,and AUC 0 ~ 24 were(390.75 ± 91.55) and(379.90 ± 84.13) ng·mL- 1·h,respectively.Relative bioavailability was(102.8 ± 7.5) %.Conclusion: The method is sensitive and convenient.No significant difference is observed among the main pharmacokinetic parameters of the test and reference tablets,demonstrating that the two formulations are bioequivalent.