Given that impurities may affect the quality and safety of
drug products, impurity identification and profiling is an integral part of
drug quality control and is particularly important for newly developed medications such as
solriamfetol, which is used to treat
excessive daytime sleepiness. Although the high-performance liquid chromatography analysis of commercial
solriamfetol has revealed the presence of several impurities, their synthesis, structure elucidation, and chromatographic determination have not been reported yet. To bridge this gap, we herein identified, synthesized, and isolated eight process-related
solriamfetol impurities, characterized them using spectroscopic and chromatographic techniques, and proposed plausible mechanisms of their formation. Moreover, we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection, revealing that its selectivity, linearity, accuracy, precision, and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for
Pharmaceuticals for Human Use. Thus, the developed method was concluded to be suitable for the routine analysis of
solriamfetol substances.