Development and Validation of Stability Indicating LC Method for Selexipag: In-Silico Toxicity Study and Characterization of its Degradation Products

An RP-HPLC method for quantifying selexipag in bulk and tablet formulations was developed and validated, and was found to be fast, sensitive, precise, accurate, and stable. Isocratic separation of Selexipag (SLG) was carried out using a Kromasil C۱۸ column (۱۵۰ mm×۴.۶ mm, ۵μm) with a mobile phase that included ۸۰:۲۰% v/v of acetonitrile and phosphate buffer (pH ۳.۰) at a flow rate of ۱.۰ mL/min. The column was maintained at ۳۰ ± ۲ °C and the wavelength for detection was set to ۲۷۰ nm. The SLG peak was detected at ۳.۳۸۰ minutes. The proposed method was linear within the ۰۵-۲۵ μg/mL range, with both drugs having a correlation value of ۰.۹۹۹. For DL, it was ۰.۶۳۳ μg/mL and for QL, it was ۱.۹۲۰ μg/mL. Although oxidative and photolytic degradation were able to stabilize SLG, acidic, alkaline, and humid heat conditions caused it to disintegrate. Liquid chromatography-mass spectrometry (LC-MS) analysis was used to verify the degradation products. The m/z of the moist heat degradation product was ۴۵۴.۵۴, while the alkali degradation product had an m/z of ۴۱۹.۵۱. Even when degradation products were present, the RP-HPLC measurements of SLG were sensitive, accurate, and exact, suggesting that the substance was stable. During the examination of SLG, it was determined that it degrades under acidic, alkaline, and moist heat conditions, whereas it is stable under oxidative and photolytic conditions. LC-MS analysis was performed to confirm the presence of degradation products.

کلیدواژه ها:

Stability-indicating RP-HPLC ، Selexipag ، C۱۸ column ، Method Development ، Method Validation