Abstract: It is a trend for illegal addition that new derivatives of known drugs are synthesized and used to avoid the statutory test. By using LTQ Orbitrap MS, an unknown derivative of sildenafil was found in a sample which was marked as traditional Chinese medicines extraction. The accurate formula of the unknown derivative was C₂₄H₃₄N₆O₄S, which was obtained based on the separating capacity of isotopic peaks of ultra-high-resolution by LTQ Orbitrap MS and accurate mass measurement. The structure of the unknown derivative was derived by comparison of the MS² spectra with those of sildenafil and thioaildenafil. The unknown derivative had the same fragment ions with sildenafil (m/z 299.11, m/z 283.11 and m/z 255.12) and thioaildenafil (m/z 113.10 and m/z 177.06) in the MS² spectra. These fragment ions were assigned with the aid of Mass Frontier^TM software. Furthermore, the assignment of one fragment ion (m/z 299.11) in literature was corrected in this paper by comparison of the accurate mass and isotopic abundance. The unknown derivative was finally identified as propoxyphenyl aildenafil by ¹H,¹³C, DEPT and HMBC NMR, which proved that it is correct for the derived structure of the unknown derivative by LTQ Orbitrap MS. This derivative was obtained by substituting the ethoxy group of the benzene ring moiety of aildenafil to the propoxy group. The proposed fragmentation pathway of propoxyphenyl aildenafil was summarized and the analytical method based on UHPLC/LTQ Orbitrap MS was developed. This method can identify the PDE-5 inhibitors and their derivatives, which could be a power tool to control the illegal addition.