(T0930-02-11) Enhancing Environmental Sustainability in the Korean Pharmacopoeia: Replacement of Carbon Tetrachloride in the Monograph for Epinephrine Injection

Purpose: Pharmacopoeias serve as national standards for pharmaceutical quality control, significantly influencing the entire pharmaceutical industry. This study aims to reduce the environmental footprint of the pharmaceutical industry by replacing the outdated test methods in the Korean Pharmacopoeia (KP) that still use reagents harmful to both human health and the environment.

Methods: To address concerns regarding exposure risks, toxicity, persistence, and significant environmental impact, we reviewed the test methods in KP for hazardous chemicals, including carbon tetrachloride, which has been designated as a substance to be avoided under the recent KP revision principle. Considering the urgency and necessity of domestic pharmaceutical supplies and the inclusion in foreign pharmacopoeias, a monograph for epinephrine injection using carbon tetrachloride in the assay method was selected, and an alternative test method to replace carbon tetrachloride was established.

Results: The current KP test method requires the use of an optical rotation test for the assay of epinephrine injection. While optical rotation analysis allows for rapid quantification with simple operation, its accuracy and precision are relatively lower compared to instrumental methods such as high-performance liquid chromatography (HPLC). We have transitioned the polarimetric method to an HPLC method to replace the use of the hazardous reagent and improve the reliability of the test results. The established method was fully validated for specificity, linearity (R² ≥ 0.99), accuracy (recovery 97.0–103.0%), precision (RSD ≤ 2.0%), and system suitability. The results confirmed compliance with established criteria: specificity (no interference), linearity in the range of 80–120% of test solution concentration (R² = 0.9998), accuracy (recovery 99.9%), and precision (RSD = 0.04%).

Conclusion: Based on these results, the revised monograph for epinephrine injection was prepared, and it is expected that this will enhance the usability of the KP by providing test method with reduced risk and contribute to enhancing the environmental sustainability of the pharmaceutical industry. Through further research, KP will revise more monographs by adopting more eco-friendly testing methods that take environmental impacts into account, thereby promoting long-term sustainability.

Acknowledgements: This research was supported by a grant (25201MFDS001) from Ministry of Food and Drug Safety in 2025.