OBJECTIVE: To establish the method for simultaneous determination of tenacissoside A, tenacissoside H and tenacissoside I in Marsdenia tenacissima. METHODS: UPLC-MS/MS method was adopted. The determination was performed on a Phenomenex Kinetex XB-C18 column with mobile phase consisted of 0.1% formic acid solution-acetonitrile (gradient elution) at the flow rate of 0.2 mL/min. The column temperature was set at 40 ℃, and sample size was 5 μL. Multiple reaction monitoring (MRM) mode was adopted with electrospray ion source as ion source, using positive ion scanning. Source jet voltage was 5 500 V, nebulizer pressure was 60 psi, heating pressure was 60 psi, curtain pressure was 20 psi and cone temp was set at 600 ℃. RESULTS: The linear ranges of tenacissoside A, tenacissoside H and tenacissoside I were 0.1-10 ng/mL (r=0.999 7), 0.025-10 ng/mL(r=0.999 5), 0.025-10 ng/mL(r=0.998 9), respectively; limited of quantation were 0.1,0.025,0.025 ng/mL,limited of detection were 0.05,0.012 5,0.012 5 ng/mL, respectively; RSDs of precision, stability and reproducibility tests were<4.0%. The recoveries were 97.67%-99.00%(RSD=0.47%,n=6), 95.00%-101.67%(RSD=2.59%,n=6), 96.67%-103.33%(RSD=2.83%,n=6). CONCLUSIONS: The method is simple, precise, stable and reproducible, and can be used for simultaneous determination of tenacissoside A, tenacissoside H and tenacissoside I in M. tenacissima.