Quantitative determination by high-performance liquid chromatography of acetylsalicylic acid and related substances in tablets.

High-performance liquid chromatography on a Zorbax C8 7-micron column (25 cm X 0.46 cm I.D.) with methanol-water-1 M phosphoric acid (59:36:5) as the mobile phase has been used for the analysis of several naturally aged batches of fourteen brands of acetylsalicyclic acid tablets. The extraction solvent is methanol, containing 2% v/v of formic acid. Salicylic acid is the main impurity. Acetylsalicylsalicylic acid is the second most important impurity, and the corresponding salicylsalicylic acid is rarely present. Buffered or dispersible tablets contain relatively more of the latter two impurities and eventually also the corresponding higher oligomers. Acetylsalicylic anhydride is always a minor impurity. Comparison is made with classical spectrophotometric methods, which are observed to be selective for salicylic acid.