3 - Degradation and Impurity Analysis for Pharmaceutical Drug Candidates

Abstract

The objective of this chapter is to give guidance with degradation and impurity structure elucidation for pharmaceutical drug candidates. Stress testing knowledge is provided as guidance in developing and executing forced degradation experiments. Impurity and degradant structure elucidation is a collaborative effort involving the degradation chemist, analytical chemist, process chemist, and/or formulator, as well as the isolation chemist, mass spectrometry and NMR experts. Updates in this second addition include: (1) the use of quality by design (QbD) model as applied to stress testing practices, expanded oxidative experimental analysis, and expanded information on predictive programs. (2) The impact of supercritical fluid chromatography as a tool for impurity isolations, along with expanded information on process workflow. (3) Mass spectrometry: additional examples and a section on the use of accurate mass information in the role of structure elucidation. (4) Expansion on the use of NMR as applied to structure characterization and elucidation. (5) In‐depth case studies that illustrate collaborative efforts made between disciplines, as well as the impact that new technologies have on the structure elucidation process.