Analytical Methodology for Characterization of Reactive Starting Materials and Intermediates Commonly Used in the Synthesis of Small Molecule Pharmaceuticals

摘要

This reviewfocuses on the analytical challenges of chromatographically characterizing sulfonate salts/esters, hydrazine functionalities, amines, boronate esters/acids, aldehydes, and sulfonate acid/esters, and acyl (acid) halides used in the synthesis of pharmaceutical drug substances. Special focus is placed on stability, degradation, and achieving the low level sensitivity required for genotoxic impurity analysis. Final pharmaceutical drug substances are designed to be stable to meet shelf life requirements, survive pharmaceutical processing into drug products, and intact delivery through the Gl and/or bloodstream to their sites of action. However, the building blocks of these APIs are not constrained by the same stability requirements and may require special considerations to be accurately analyzed.