Abstract: To establish an LC-MS/MS method for the determination of agomelatine in human plasma and to study the pharmacokinetics in Chinese healthy volunteers following oral administration of agomelatine tablets. 72 volunteers were administered with single oral dose of 25 mg of agomelatine. The plasma concentration of agomelatine was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by Phoenix WinNonlin 6. 3. 0. The calibration curve of agomelatine was linear over the range of 0. 051 3-10. 38 ng/mL(r=0. 999 4). The lower limit of quantification of agomelatine was 0. 051 3 ng/mL. Both intra- and inter-day RSD were less than 15%. The main pharmacokinetic parameters were as follows: c_max was(13. 25±15. 78)ng/mL; t_max was(0. 68±0. 41)h; AUC_last was(14. 00±19. 26)ng/mL ·h; AUC_inf was(14. 14±19. 35)ng/mL ·h and t1/2 was(0. 78±0. 44)h. The LC/MS/MS method was convenient, precise and reproducible. It can be used for the determination of agomelatine in human plasma and its clinical pharmacokinetic studies.