Chapter 18 - Integrity and Purity

Abstract

The quality of materials used in drug discovery plays a crucial role in the success of discovery research. If there is an unknown problem with the quality of the material, the viability of the biological and absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) property studies will be in question or will confuse the discovery project team. For this reason, integrity and purity profiling of discovery compounds can be as important as other physicochemical and metabolic properties of the compounds. Medicinal chemists deal directly with integrity and purity for each new compound and batch that is synthesized. This is commonly accomplished using nuclear magnetic resonance (NMR) and mass spectrometry (MS) for structure verification and high-performance liquid chromatography (HPLC) for purity checking. Compounds come into discovery biology and ADME/Tox laboratories from many sources. It is prudent to verify the quality of compounds in order to produce an accurate structure–activity relationship (SAR). Integrity and purity can affect assessment of the properties of compounds. There are several causes for problems with integrity and purity of some materials. Moreover, this chapter provides an example of potential integrity and purity problems of compound libraries. Without integrity and purity profiling, discovery experiments may proceed at risk.