Active pharmaceutical degradation products

Toxic Decomposition Products In situations where the content of the API in a drug product is well above 90% as indicated above, the formation of toxic degradation products within the shelf life (which may cause untoward effects to the patients) may warrant the reassignment of a different expiration date or recall of the drug product in question. Consequently, the pharmaceutical industry is often concerned with both the amount as well as the nature of the degradation products. The formation of toxic products is particularly problematic with protein drugs which may maintain therapeutic activity after deliberate modification or pertubation of molecular structure in a domain removed from that associated with therapeutic activity... 

In Section 8.2, the aim of analysis is emphasized especially for the API (active pharmaceutical ingredient) and the drug product. The workflows and the rationale at major decision points during synthetic processing steps where HPLC can be applied in process development are elaborated upon. For example, a fast method is needed to monitor reaction conversion of two components. However, a more complex method would be needed for stability-indicating purposes where multiple degradation products, synthetic by-products, and excipient peaks need to be resolved from the active pharmaceutical ingredient. 

Availability of the Finalized Pharmaceutical Active Ingredient (API), Known Degradation Products, By-products and Reference Standards... 

Padl, T. and E. Liptak-Csekey. 1990b. Toxic Degradation Products of Active Ingredients A New Target for Quality Control of Pharmaceutical Preparations. Acta Pharmaceutica Jugoslavica 40 199-206. 

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