Development of Certified Reference Materials for Pharmaceutical Impurities using Quantitative NMR

Abstract

Pharmaceutical impurities are unintended substances in finished drug products, that may arise during manufacturing, degradation, or through interactions with excipients or packaging materials. As they are neither the drug substance nor an excipient, they can potentially impact safety, efficacy, and overall quality of the product. We describe the synthesis routes of different paclitaxel related impurities. Paclitaxel is a highly oxygenated taxane diterpenoid with a complex tetracyclic core and eleven stereocenters. We utilize quantitative nuclear magnetic resonance (qNMR) as a primary method for value assignment, complemented by comparison to compendial standards when available and developed certified reference materials (CRM) in accordance with ISO 17034, ensuring traceability to the SI (Système international d’unités).