Simultaneous relative UV response determination of known liquid drug product degradants by NMR spectroscopy

Abstract

Determination of impurity level in weight percent against the claimed active pharmaceutical ingredient (API) in a drug product is of critical importance in drug development. However, authentic material used to determine relative UV response factor (RRF) for impurity quantitation is sometimes not available or not stable. In a particular drug product liquid formulation, three degradants, including one unstable impurity, are consistently observed in stability studies. Here we describe the application of NMR spectroscopy to assist in the determination of RRFs, simultaneously, for all three degradants directly from degraded drug product extracts. This technique was not only effective in determining RRF of an unstable substance, but also in defining RRFs of multiple degradants from a single drug product sample. Overall, this study continues to demonstrate the capabilities of NMR for impurity quantitation in drug development.