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

Vijaya Madhyanapu Golla, Rahul Khemchandani, Sowmya Chaganti, Gananadhamu Samanthula
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Abstract

Deucravacitinib, 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.
高效液相色谱法和液相色谱-质谱法分离和表征去氯伐他汀的水解降解产物
Deucravacitinib, SOTYKTU 最近于 2022 年获批用于治疗银屑病。本研究试图对该药物在水解、氧化、热和光解等应激条件下形成的降解产物进行鉴定和表征,并研究该药物在各种应激条件下的降解动力学。以乙酸铵(pH 4.75)缓冲液为流动相,乙腈为溶剂 B,Phenomenex Gemini, C-18 (250 × 4.6 mm, 5µ)色谱柱为固定相,建立了一种高效液相色谱法分离去氯伐替尼及其降解产物。进样量、流速和检测波长分别优化为 10 µL、1.0 mL/min 和 254 nm。在 5 至 150 µg/mL 的 deucravacitinib 浓度范围内验证了该方法的准确度、精密度、线性、稳健性和选择性。利用液相色谱-串联质谱对降解产物的结构进行了表征,在电喷雾正离子模式下,降解产物在 m/z 358.1805 处出现质子化分子离子峰。对 deucravacitinib 及其降解产物进行的硅学致突变性测试结果呈阳性,触发了这两种结构的致突变性警报,而硅学毒性研究未产生任何结构警报。
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