Impurity Profiling in Drug Development

Impurities in pharmaceuticals are unwanted chemicals that remain with the active pharmaceutical ingredients (APIs) or develop during formulation or upon aging of both API and formulation. In the pharmaceutical industry, an impurity is considered as any other inorganic or organic material, or residual solvents other than the drug substances, or ingredients, that arise out of synthesis or unwanted chemicals that remains with APIs. The presence of these unwanted chemicals even in trace amount may influence the efficacy and safety of pharmaceutical product.

Impurity profiling includes identification, structure elucidation and quantitative determination of impurities and degradation products in bulk drug materials and pharmaceutical formulations. Impurity profiling has gained importance in modern pharmaceutical analysis due to the fact that unidentified, potentially toxic impurities are hazardous to health and in order to increase the safety of drug therapy, impurities should be identified and determined by selective methods.

Impurities in formulated products and APIs are regulated by various regulatory authorities such as ICH, USFDA, Canadian Drug and Health Agency that are emphasising the purity requirements and the identification of impurities in APIs. Identification, quantification, and control of impurities in API and the drug product are critical in drug development. Organic impurities are often free radicals from by-products, intermediates, or degradation products. Inorganic impurities include transition metals, reagents, and ligands. Identification of impurities is done by variety of Chromatographic and Spectroscopic techniques, either alone or in combination with other techniques.

Electron Paramagnetic Resonance (EPR) spectroscopy is the only technique for the direct and non-invasive detection, identification and quantification of paramagnetic impurities (organic free radicals and transition metals). EPR is able to detect traces of impurities down to parts per billion levels.

EPR spectroscopy detects and identifies traces of transition metals, monitors drug degradation processes that produce and involve free radicals and observes the production of free radicals catalysed by transition metals or other impuritie.