Chapter 25 - Liquid chromatography in the pharmaceutical industry

Abstract

The primary focus of separation scientists supporting pharmaceutical drug development is to provide evidence of safety of medicines administered to patients and volunteers during clinical trials. This critical objective is achieved through application of various forms of state-of-the-art separation science techniques, often combined with spectroscopic detection techniques. The role of separation science, which plays a pivotal role in all phases of pharmaceutical drug development, is extensively described in the introductory part of this contribution. The early stages of pharmaceutical drug development typically require chromatographic techniques that provide very high resolution. This is essential as, at this stage of development, a relatively large number of process-related impurities, synthetic intermediates, and degradation products must be separated to characterize starting materials and products of chemical synthesis. In the first part of this chapter, we focus on multiple ways of enhancing chromatographic resolution for the purposes of satisfying these early development demands. In the later stages of the drug development process, when the manufacturing processes are being qualified, the emphasis shifts from resolution to speed, ruggedness, and robustness. The second part of this chapter provides an overview of useful tools and techniques that may be applied in such a setting. In the final part of this chapter, we focus on novel trends in chromatographic method development related to the analytical quality by design initiative. In this section, we also provide references to some recent research aimed at structure-driven prediction of chromatographic retention which can be used to drive early stages (scoping) of method development.