ABSTRACT A robust and stability‐indicating ultra‐high‐performance liquid chromatography method was developed and validated for the quantification of mirdametinib and its related impurities, along with the identification of degradation products using liquid chromatography–tandem mass spectrometry. Chromatographic separation was achieved on an Acquity bridged ethylene hybrid C18 column (2.1 × 50 mm 2 , 1.7 µm) using a mobile phase consisting of acetonitrile and triethylamine buffer adjusted to pH 3.0 with formic acid in a 30:70 (v/v) ratio, at a flow rate of 0.4 mL/min with ultraviolet detection at 235 nm. The method was validated in accordance with International Council for Harmonisation guidelines Q2(R1) for specificity, accuracy, precision, linearity, robustness, and detection limits. Linearity was established for mirdametinib in the range of 25–150 µg/mL and for related impurities in the range of 0.5–5.0 µg/mL, with correlation coefficients greater than 0.999. The limits of detection and quantification (0.50 and 1.65 µg/mL, respectively) demonstrated high method sensitivity. Forced degradation studies performed under acidic, alkaline, oxidative, reductive, thermal, photolytic, and hydrolytic conditions revealed four major degradation products. Mass spectrometric analysis confirmed the accurate mass and fragmentation pathways of these degradation products, establishing the stability‐indicating capability of the method. The validated method is sensitive, precise, and reproducible, making it suitable for routine quality control and stability evaluation of mirdametinib in bulk drug substances and pharmaceutical formulations.
Bodapati et al. (Sun,) studied this question.