The stability and degradation pathways of phenyl salicylate (PS) in 50 v/v% aqueous ethanol were investigated over the pH range of 3.2-8.4. The experiments were performed at three different temperatures (5, 23 and 50°C) for four months by the use of high performance liquid chromatography. The degradation of PS was observed as a pseudo first-order kinetics not only in the alkaline region but in the acidic region and shown to proceed via transesterification (k
1) and hydrolysis (k
2) processes. The transesteified product, ethyl salicylate (ES), further underwent hydrolysis (k
3)(k
1>k
2>k
3). On the basis of kinetic studies, it was found that the degradation rate of PS decreased with decreasing pH and temperature. The half-lives of PS at pH 6.3 were 6.6d (50°C), 178d (23°C) and 2934d (5°C), respectively, and PS was stable at below ca. pH 4. On the other hand, PS in 100% ethanol also underwent the breakdown to ES by k
1 process and its half-lives were 2.5d (50°C), 31.5d (23°C) and 257d (5°C), respectively. The present results is useful for the integrity of pharmaceutical formulations and delivery profiles.
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