조영엄 (대웅제약)

황하나 (대웅제약)

조영엄 (대웅제약)

황하나 (대웅제약)

이소영 (대웅제약)

정지인 (대웅제약)

김관영 (대웅제약)

Stress degradation studies are essential for predicting potential degradation products under worst-case storage conditions, supporting early risk assessment and ensuring compliance with regulatory guidelines. Ruxolitinib, a selective Janus kinase (JAK) 1 and 2 inhibitor used to treat myelofibrosis and polycythemia vera, requires such evaluation to ensure its stability and safety. Structurally, Ruxolitinib is a small molecule containing a substituted pyrrolo[2,3-d]pyrimidine core. Its molecular formula is C₁₇H₁₈N₆ with an exact mass of 306.1592 Da.

Under stressed storage conditions (50 °C/85% RH) for two months, two unknown impurities were observed in Ruxolitinib tablets. One impurity reached a level of 0.77%, while the other was present at 0.22%, both exceeding the identification threshold defined in ICH Q3B. These degradation products were subsequently subjected to tentative structural elucidation using 2D-LC/QTOF-MS. High-resolution MS analysis revealed that the major impurity exhibited a protonated molecular ion at m/z 327.1567, while the minor impurity was detected at m/z 311.1616. The results contribute to a better understanding of the stability profile of Ruxolitinib under humid and thermal stress conditions.