Cyclooxygenase-2 (COX-2) is an enzyme responsible for inflammation and pain. Etoricoxib is the most recent selective (COX-2) inhibitor that has a higher COX-2 selectivity than the other COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs), which significantly improves its gastric safety profile. The current therapeutic indications of etoricoxib includes the treatment of several painful conditions, such as osteoarthritis, acute gout, ankylosing spondylitis, and rheumatoid arthritis. To the best of found knowledge, no decent method has been reported that can be used for the routine determination of etoricoxib and additives in pharmaceutical suspensions by a single, rapid and cost-effective run of HPLC, using an UV-Vis detector. Earlier reported methods, such as liquid chromatography-mass spectrometry (LC-MS), high performance thin layer chromatography (HPTLC), capillary zone electrophoresis, and ultra performance liquid chromatography (UPLC), are all tedious and time consuming. A reversed phase high performance liquid chromatography (RP-HPLC) was used as a first reported single run method to achieve developed and validated simultaneous determination for sodium saccharin, vanillin, methyl paraben, etoricoxib, and butyl paraben, in prepared oral suspensions of etoricoxib. Reversed phase column of octadecylsilane (ODS) C18 with isocratic mobile phase containing methanol, and phosphate buffer of pH 6 in a ratio of 70:30 (v/v). Celecoxib is used as an internal standard at a detection wavelength of 215 nm. This method separates the analytes in a total running time less than 13 min. Linearity is obtained in the calibration curve for all analytes with a R2 value of > 0.999. Furthermore, beta-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were added, either alone or combined, to prevent the crystal formation, and any unpleasant taste of etoricoxib in oral formulations. After testing both HP-β-CD and β-CD at 3% w/w for each, the results showed that HP-β-CD is more efficient in preventing the crystal formation of etoricoxib in suspensions at room temperature than β-CD is.