人血浆中阿戈美拉汀浓度的测定及其药代动力学

建立测定人血浆中阿戈美拉汀浓度的LC-MS/MS方法，测定单剂量口服25 mg阿戈美拉汀片后其在中国健康受试者体内的血药浓度，利用Phoenix WinNonlin 6.3.0软件计算药代动力学参数。该方法中阿戈美拉汀浓度的线性范围为0.051 3~10.38 ng/mL(r=0.999 4)，最低检测浓度为0.051 3 ng/mL。日内、日间精密度测定RSD均小于15%。单次口服给药后，阿戈美拉汀的c_max为(13.25±15.78)ng/mL，t_max为(0.68±0.41)h，AUC_last为(14.00±19.26)ng/mL·h，AUC_inf为(14.14±19.35)ng/mL·h，t_1/2为(0.78±0.44)h。本方法简便、准确、重现性好，可用于阿戈美拉汀血药浓度的测定及其人体药代动力学研究。

Determination of agomelatine in human plasma by LC-MS/MS:application to a pharmacokinetic study in Chinese volunteers

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.