Abstract: An LC-MS/MS method was established for the determination of potassium oxonate (Oxo) in human plasma and urine,the pharmacokinetics of Oxo was investigated in advanced gastric cancer patients after single and multiple administration of tegafur,gimeracil and oteracil potassium capsule (S-1),and the situation of drug accumulation after multiple administration was evaluated.For multiple administration,12 gastric cancer patients were treated with S-1 according to the body surface area (BSA) as follows:for single administration,patients were treated with 60mg S-1 after breakfast;for 28-day consecutive administration,a dose of 60mg S-1 was treated after breakfast,and the dose of 60mg after supper for BSA≥ 1.5 m ² or 40mg for 1.25m ² 2 respectively.Then the Oxo concentration in human plasma and urine was determined,and the pharmacokinetic characteristics and drug accumulation were evaluated.The calibration curves of Oxo were linear over the concentration ranges of 2-400 ng/mL in plasma and 0.02-10 μg/mL in urine.After single-dose administration of S-1,(1.7±1.2)% of Oxo was excreted in the form of prototype in urine within 36 h.The main pharmacokinetic parameters were as follows:the c_max was (110.5±100.8)ng/mL,t_1/2 was (3.4±1.4)h,t_max was(2.2 ±0.7) h,respectively.For the multiple administration,the c_ss-av and degree of fluctuation (DF) of Oxo were (110.8±108.0) ng/mL and 2.4±0.8,respectively.In the 28-day consecutive regimen,no significant chang in pharmacokinetic characteristics or drug accumulation of Oxo was observed,the safty of that multiple administration of S-1 in clinical application was confirmed.Compared with the data in literatures,the main pharmacokinetic parameters of Oxo in Chinese patients proved to be similar with those in other races.