Mass Spectrometry in the Characterization of Complex Drugs

Mass spectrometry is an essential tool for the characterization of complex drug products. Characterization of complex drug products presents unique challenges, as these products are often difficult to characterize not only because of the complexity imparted by their heterogeneity but also based on their size. Many modern mass spectrometers afford sufficiently high resolution and mass accuracy that allow for many of the individual components within these complex mixtures to be distinguished. Coupling mass spectrometry with liquid chromatography or other separation techniques can enhance the sensitivity and selectivity to facilitate improved identification and relative quantitation of the species present in these complex products. Tandem mass spectrometry can provide additional structural information to better determine the identity and connectivity of specific molecules based on the analysis of the different fragmentation pathways observed. Differential analysis of these intricate datasets can help to distinguish between diverse sources of complex mixture drugs. In this chapter, an overview of the importance of mass spectrometry in the characterization of complex drugs will be provided. As a variety of modern mass spectrometry instruments are available, those mass spectrometers most amenable to complex drug analysis will be discussed. Selected case studies where the use of mass spectrometry was applied to complex drug products, including for the analysis of conjugated estrogens, glatiramer acetate, and naturally derived peptide products will be presented. While these case studies report on the capabilities of mass spectrometry-based approaches based on currently available technologies, the potential of emerging techniques to improve complex drug characterization, as well as any limitations associated with their implementation, will also be discussed.