Mass spectrometry-based structure elucidation of small molecule impurities and degradation products in pharmaceutical development

Abstract Mass spectrometry (MS) has played a critical role in the identification of unknown small molecules for many years. As such, it is also a pivotal technique in the structure elucidation of drug impurities and degradation products during pharmaceutical development. In this review we discuss the regulatory expectations and some general practices regarding the identification of process-related impurities and degradation products of small molecule therapeutics; with an emphasis on the role of MS in this process. Recent advances in instrumentation, facilitating MS-based structure elucidation are covered. Over the last few years, many software tools have been developed that aid in the annotation and identification of small molecules by their precursor and product ion spectra. This evolution is promising since it is key to alleviate the current data interpretation bottleneck. The main approaches used in these bioinformatics tools are critically surveyed. This review aims to give meaningful insight in the current state of MS-based structure elucidation of small molecule impurities and degradation products.