Characterization of 12 Unknown Photodegradation Impurities of Tunlametinib Capsules Using Liquid Chromatography Coupled With ion Trap/Time-Of-Flight Mass Spectrometry.

RATIONALE: In March 2024, tunlametinib capsules, a Class 1 new drug (referring to active pharmaceutical ingredients and formulations not previously marketed either nationally or globally), were approved in China for treating patients with advanced melanoma and neuroblastoma RAS viral oncogene homologue mutations who experienced disease progression or intolerance to anti-PD-1/PD-L1 therapy. Risk assessment of impurity profiles is essential for drug safety and efficacy in clinical applications. This study characterized impurity profiles in tunlametinib capsules induced by photodegradation.

METHODS: Initial high-performance liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (HPLC/IT-TOF MS) in positive ion mode was first performed to determine the m/z values of protonated ions and predict the formulas of the detected impurities. Subsequent LC-MSn analyses (n = 2-4) of target compounds elucidated comprehensive structural features.

RESULTS: Twelve previously unidentified photodegradation impurities in tunlametinib capsules were characterized using HPLC/IT-TOF MS.

CONCLUSIONS: Structural elucidation of 12 previously uncharacterized photodegradation impurities was achieved through HPLC/IT-TOF MS. These findings establish a scientific foundation for refining quality specifications of tunlametinib.