ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF RESMETIROM USING UV SPECTROSCOPY AND RP-HPLC

*Shish A. Khan, Sabeeha A. Kamal, Amaan Khan, Megha Pandagale

The current research focuses on developing and validating precise, straightforward UV spectrophotometric and reverse-phase high-performance liquid chromatographic (RP-HPLC) methodologies for quantitative determination of Resmetirom in pure form. The UV spectrophotometric method was established using a phosphate buffer and acetonitrile mixture (50:50 v/v) as solvent. Maximum absorbance occurred at 225 nm. The linearity range was determined to be 16-24 microgram per millilitre, and the method was validated for parameters including linearity, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ) according to ICH guidelines. For the RP-HPLC procedure, separation was achieved using a Phenomenex Kinetex XB-C18 column (150 x 4.6 mm, 5 μm) with phosphate buffer and acetonitrile (60:40 v/v) as mobile phase, at a flow rate of 1.0 mL/min and detection at 225 nm. Resmetirom exhibited a retention time of 3.41 minutes. The method demonstrated excellent linearity (R² = 0.9998), precision (intra-day %RSD = 0.94, inter-day %RSD = 1.94) and accuracy (recovery values of 100.07%, 100.64% and 100.07%). LOD and LOQ were determined as 0.56 μg/mL and 1.69 μg/mL respectively. Both methodologies satisfied validation requirements, with the HPLC method showing superior accuracy, making it particularly suitable for routine quantitative analysis. These developed methods can be utilized to evaluate Resmetirom efficacy, as analytical data and validated results are currently scarce in the literature.