Abstract: The development of a rimantadine hydrochloride purity certified reference material (CRM) (GBW 10262) was carried out using two independent methods: the mass balance (MB) method and quantitative nuclear magnetic resonance (qNMR) spectroscopy. Critical aspects of the CRM development process, including homogeneity, stability, calibration, and uncertainty, were systematically investigated. The purity of rimantadine hydrochloride CRM, as determined by both methods, was found to be 99.7%±0.3% (k=2). The CRM demonstrated excellent homogeneity, maintaining long-term stability for 20 months, and short-term stability for seven days at 50°C. The study also involved a thorough assessment of uncertainty sources, including characterization, stability, and homogeneity. The rimantadine hydrochloride CRM will support activities such as instrument calibration, method validation, and quality and safety risk monitoring.