The breakdown of aspirin in tablet formulations containing phenylephrine was found to result in a concurrent loss of phenylephrine activity. Specific functional group analysis of the secondary amine function on phenylephrine was necessary to follow degradation in tablet formulations. Analyses with methods based on the phenolic function of phenylephrine did not show similar activity loss. With the use of thin-layer chromatography and comparative chromatograms with synthetic acetylated phenylephrine derivatives, three acetylated phenylephrine degradation products could be identified in tablet formulations. At room temperature the primary degradation pathway was the acetylation of the secondary amine function, but at elevated temperatures, acetylation was found to have progressed to phenylephrine's phenolic and alcoholic groups.