Separation and characterization of hydrolytic degradation product of deucravacitinib by validated high‐performance liquid chromatography method and liquid chromatography‐mass spectrometry

Abstract

AbstractDeucravacitinib, SOTYKTU was approved recently in the year 2022 to treat psoriasis. The present work attempts to identify and characterize degradation products formed when the drug is exposed to hydrolytic, oxidative, thermal, and photolytic stress conditions as well as to study the kinetics of the drug's degradation under various stress conditions. A high‐performance liquid chromatography method was developed for the separation of deucravacitinib and its degradation product comprising mobile phase of ammonium acetate (pH 4.75) buffer as solvent A and acetonitrile as solvent B and Phenomenex Gemini, C‐18 (250 × 4.6 mm, 5µ) column as stationary phase. Injection volume, flow rate, and detection wavelength for the method were optimized as 10 µL, 1.0 mL/min, and 254 nm, respectively. Accuracy, precision, linearity, robustness, and selectivity were found to be acceptable when validated in the concentration range between 5 and 150 µg/mL of deucravacitinib. The structure of the degradation product was characterized using liquid chromatography‐tandem mass spectrometry which shows a protonated molecular ion peak at m/z 358.1805 in the electrospray ionization positive mode. In silico mutagenicity tests yielded positive results for deucravacitinib and its degradation product, triggering an alarm for mutagenicity for both structures, whereas in silico toxicity studies did not generate any structural alerts.