An impurity is defined by the United States Pharmacopeial (USP) as “any component of a drug substance that is not the chemical entity defined as the drug substance” and a drug product impurity is “any component that is not a formulation ingredient”. Impurities in an active pharmaceutical ingredient (API) or drug product may arise as a result of synthetic/manufacturing processes, degradation, storage conditions, containers, excipients, or contamination. According to the definitions of International Council for Harmonization (ICH), Food and Drug Administration (FDA), and USP, impurities are classified into degradation-related impurities (DRIs), process-related impurities (PRIs), residual solvents, and heavy metals.
Regardless of the type of impurity, the presence of an impurity may affect the quality, safety, and efficacy of a drug product. API-related impurities are potentially genotoxic, mutagenic, and carcinogenic due to their structure-activity relationship (SRA). In API-related impurities, one type is the impurities generated by degradation of API itself under specific storage conditions, such as oxidation, dehydration, carbon dioxide removal. The other type is generated due to the interaction between APIs and excipients, container, or residual impurities in excipients, reagents, or solvents. Excipients or the residual impurities in excipients (such as active peroxides or high-water content in povidone or polyethylene glycol (PEG), antioxidants in magnesium stearate, benzaldehyde in benzyl alcohol) are likely to lead to instability of APIs and pharmaceutical products. In addition, initiators/catalysts, storage stabilizers, antioxidants, processing aids, light stabilizers, etc., may also pose uncertain risks to the stability or quality of products.
One of the keys to the development of APIs and manufacturing process is the determination of a drug substance impurity profile. Analytical monitoring and controlling of impurities is often challenging and is conducted under the regulatory requirements. The exact identification and quantification of impurities in pharmaceuticals is essential for documentation of registration of pharmaceutical products, and impurity reference standards play a vital role. Amerigo Scientific provides more than 1,000 impurity reference standards for drug development and API manufacturing.