A quality evaluation strategy for multi-sourced active pharmaceutical ingredient (API) starting materials

Abstract

Establishing appropriate impurity specifications for active pharmaceutical ingredient (API) starting materials is an important component of the commercialization and registration of an API. Multiple sources and routes of manufacture of starting materials and the capability of the API synthetic process for tolerating impurities introduced with starting materials must be understood. A strategy for purity method development and use test evaluation of starting materials to aid in establishing quality requirements is described. Phenyl methyl amino propanol (PMAP), a starting material that may be used for fluoxetine hydrochloride and atomoxetine hydrochloride, is used to illustrate the quality evaluation strategy. Knowledge of actual and potential synthetic routes was used to predict potential impurities and guide purity method development. Multiple analytical methods that were semi-orthogonal in the nature of impurity retention (ion-pairing, ion interaction and hydrophilic interaction chromatographic modes) along with use tests were investigated.