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 remain with APIs. The presence of these unwanted chemicals even in trace amounts may influence the efficacy and safety of the 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 the 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.
Recent trends in the impurity profile of pharmaceuticals
Impurities in formulated products and APIs are regulated by various regulatory authorities such as the International Conference on Harmonization (ICH), the United States Food and Drug Administration (FDA), Canadian Drug and Health Agency (CDHA) that are emphasizing 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.
Various methods are used to isolate and characterize impurities in pharmaceuticals, such as capillary electrophoresis, electron paramagnetic resonance, gas-liquid chromatography, gravimetric analysis, high-performance liquid chromatography, solid-phase extraction methods, liquid-liquid extraction method, Ultraviolet Spectrometry, infrared spectroscopy, supercritical fluid extraction column chromatography, mass spectrometry, Nuclear magnetic resonance (NMR) spectroscopy, and RAMAN spectroscopy. Among all hyphenated techniques, the most exploited techniques for impurity profiling of drugs are Liquid Chromatography (LC)-Mass Spectroscopy (MS), LC-NMR, LC-NMR-MS, GC-MS, and LC-MS.
Identification of impurities is done by a 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. This reveals the need and scope of impurity profiling of drugs in pharmaceutical research.