Solving impurity/degradation problems: Case studies

Publisher Summary The chapter presents case studies related to solving impurity/degradation problems. The chapter presents guidance for isolating and identifying process-related impurities and degradation products from pharmaceutical drug candidates using actual case studies. Impurity and degradant structure elucidation is a collaborative effort involving the analytical chemist, process chemist and/or formulator, as well as the degradation, mass spectrometry, and nuclear magnetic resonance (NMR) experts. The process described in this chapter uses a designed approach for the impurity and/or degradant identification, which focuses on efficiency so that the success of data collection is maximized and project time lines are met. There are a number of activities other than collecting experimental data, even though the experiments are central to the process. Some of these key activities include collecting project background information prior to pursuing experimental work, asking the right questions, and meeting with project analysts and structure elucidation experts. The activities associated with the overall process are captured in the process flowchart presented. One of the most important aspects of the project that determines approach is where the pharmaceutical drug candidate is in the drug development time line. NMR spectroscopy is used as a complementary technique to liquid chromatography/mass spectrometry (LC/MS). The chapter presents several case studies related to scaled-up oxidative degradation and isolation using solid-phase extraction and preparative high-performance liquid chromatography (HPLC), scaled-up oxidative degradation, preparative HPLC, and characterization by LC/MS and NMR, scaled-up light degradation and LC/MS and NMR characterization, and others.