Quantitative NMR assay for aspirin, phenacetin, and caffeine mixtures with 1,3,5-trioxane as internal standard.

The method for (1)H NMR determination of aspirin, phenacetin and caffeine (APC) mixtures has been improved by the use of 1,3,5-trioxane as an internal standard. The trioxane absorption occurs in a peak-free region of the spectrum and produces no interferences with any of the analytes. Compared to the original method with caffeine as an external standard, the present method appears to offer better accuracy and precision. Average errors relative to the correct results were: aspirin, 1.0%; phenacetin, 0.8%; and caffeine 1.8%, for known standard mixtures. Coupling constants, (1)J((13)CH), were determined for the methyl groups of aspirin and caffeine and for the trioxane methylene group to clarify potential (13)C satellite interferences.