This study aimed to develop a rapid and reliable reversed-phase high-performance liquid chromatography (RP-HPLC) assay method for the quality control of amiodarone hydrochloride tablets, an essential medicine, to replace existing inefficient analytical procedures. The objective was to validate the developed method according to the ICH Q2(R2) guideline to demonstrate its suitability for quality control testing. Chromatographic separation was performed on a Gemini® C18 column (4.6 × 250 mm, 5 µm). The analysis time was significantly reduced by optimizing the mobile phase through the addition of triethylamine and adjustment of the organic solvent ratio. Under the optimized conditions, the retention time of amiodarone was approximately 5.5 minutes, achieving an efficiency gain by reducing the analysis time by over 80% compared to the conventional method. The method validation results met all acceptance criteria for system suitability, specificity, accuracy, precision, and robustness. Excellent linearity was confirmed with a correlation coefficient greater than 0.999 over a concentration range of 60–140% of the standard solution. Furthermore, the method demonstrated specificity by effectively separating the active pharmaceutical ingredient without interference from excipients. In conclusion, the established analytical method is time- and cost-effective, highly reproducible, and can be effectively applied to the quality control of amiodarone hydrochloride formulations.