Abstract: OBJECTIVE To establish a LC/MS test method for determining the concentration of thiorphan(TP, the active metabolite of racecadotril) in the human plasma, the pharmacokinetics and bioequivalence of two racecadotril pulvis(10 mg, 30 mg) and racecadotril granule(10 mg) in healthy human body. METHODS A single oral dose 300 mg of three preparations was randomly given to 18 healthy volunteers in a three cycle duplex 3×3 latin square crossover design. The concentration of TP in plasma, which was an active metabolite of racecadotril, was determined by LC-MS at different time. The pharmacokinetics parameters were calculated and the bioequivalence of three formulations were evaluated by DAS program. The p-BPB was added to the plasma as a derivative agent to achieve a stable TP-derivative. The TP-derivative was then extracted from the plasma using ethyl acetate. The method used telmisartan as internal standard material. In the test method, Zorbax SB-C₁₈(150 mm×2.1 mm, 5 μm) was used as chromatogram column, 5 mmol?L^-1 ammonium formate(adjust pH to 3.0 with formic acid)-acetonitrile (45∶55) as mobile phase, the flow rate 0.2 mL?min^-1, ESI+SRM as detector. RESULTS The analytical method validation of TP was as follows: linear range 6.28-1 256 ng?mL^-1, detection limit 6.28 ng?mL^-1, extraction rate 77.5%-80.4%, precision of within and between day(RSD) both <15%. The main pharmacokinetic parameters of racecadotril pulvis(10 mg), racecadotril pulvis(30 mg) and reference granules were as follows: T_max (1.8±1.2), (1.9±1.3) and (0.7±0.2)h, t_1/2 (1.4±0.4), (1.2±0.7) and (1.1±0.8)h, C_max(802.0±356.5), (804.2±459.8) and (845.6±285.8)ng?mL^-1, AUC_0-8(1 617.0±532.6), (1 628.9±672.1) and (1 621.0± 532.2)ng?h?mL^-1, AUC_0-∞ (1 690.8±567.2), (1 673.8±681.7) and (1 649.4±561.4)ng?h?mL^-1, respectively. The relative bioavailability of 2 test pulvis versus reference granule were 99.8% and 100.5%, respectively. CONCLUSION The test method of determining the concentration of TP in human plasma is sensitive and precise. Study shows that the two test racecadotril pulvises are bioequivalent to reference granule.