Quantitative characterization and in silico toxicity assessment of degradation products from the dopamine and norepinephrine reuptake inhibitor solriamfetol

Solriamfetol, a dopamine and norepinephrine reuptake inhibitor (DNRI) indicated for the treatment of excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea, was subjected to comprehensive forced degradation studies in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q1A(R2) guidelines. The drug exhibited moderate degradation under acidic and basic stress conditions, while stable under thermal, photolytic, peroxide, and humidity stress environments. A simple, precise, and reliable stability-indicating High-Performance Liquid Chromatography (HPLC) method was developed for the effective separation of solriamfetol from its three degradation products (DPs), DP-1, DP-2 & DP-3. Chromatographic separation was achieved using a zorbax Stable Bond cyano column with a mobile phase consisting of 10 mM potassium dihydrogen phosphate buffer (pH 3.0) and acetonitrile under gradient elution. The flow rate was set at 0.7 mL/min, and detection was performed at 210 nm using a photodiode array (PDA) detector. Degradation products were isolated and structurally characterized using Nuclear Magnetic Resonance (NMR) spectroscopy, Mass Spectrometry (MS), and Fourier Transform Infrared Spectroscopy (FTIR), allowing for the elucidation of their chemical structures. The developed HPLC method was validated according to ICH guidelines and demonstrated excellent specificity, linearity, precision, and accuracy. This robust, stability-indicating method is suitable for routine quality control and effectively quantifies both known and unknown impurities in solriamfetol.