Analytical approach of elemental impurities in pharmaceutical products: A worldwide review

Elemental impurities may occur in pharmaceutical products under different conditions. Impurity composition includes many types of species: metals and non-metals, which can be essentially toxic, due to their direct health damage potential, and those essential elements or compounds, which play a physiological role in the human body in defined levels. The essential ones may develop an illness profile or a non-desirable situation, since their concentrations exceed permitted and tolerable limits. Inorganic contamination in pharmaceuticals has been observed in several countries. A high number of reports on metal contamination in natural products, traditional eastern medicines, herbal medicines and medicinal plants have been presented, especially with lead, cadmium, mercury and arsenic. A simple explanation to this fact is mainly related to metal deposition in the soil, water contamination, fertilizer and pesticide poisoning. Synthetic products are faced to catalyst deposition, water contamination, glassware impurities, contaminated raw materials and excipients, as well as uncontrolled manufacturing processes. Several analytical methods have been developed and improved for years, allowing the application of better strategies to evaluate metal contamination in pharmaceutical products. Spectroscopy techniques are used by industries in routine investigations, and can also be improved to attend different types of matrices and materials. In Brazil, the Brazilian Pharmacopeia and National Health Surveillance Agency are the available guide and institution, respectively, onto which the investigation of elemental impurities is based. In the international scenario, The United States Pharmacopeia (USP), The European Pharmacopeia (EU), The European Medicine Agency (EMA) Guideline and The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) Guideline are the four most important and complete manuals for the evaluation of impurities in pharmaceutical products, active pharmaceutical ingredients (APIs), raw materials and intermediates in the present days. A great amount of scientific research about inorganic impurities in pharmaceuticals has been conducted in recent years, but it still remains below the strategies of analytical applications due to the many possibilities of contamination. The continuous work on this theme, regulated by international agencies, is the best way to improve the quality of pharmaceutical products and to ensure safety in their use. The objective of this paper is to summarize spectroscopy techniques applied to inorganic evaluation in pharmaceuticals, considering the limits of element exposure to human beings reported by national and international references.

Automated summary

Elemental impurities can be present in pharmaceutical products, and they can be either toxic or essential elements. Metal contamination, especially with lead, cadmium, mercury, and arsenic, is commonly observed in natural products, traditional medicines, and herbal medicines. Inorganic contamination in pharmaceuticals can be caused by factors such as soil deposition, water contamination, and manufacturing processes. Analytical methods, especially spectroscopy techniques, have been developed and improved to evaluate and monitor metal contamination in pharmaceutical products. International guidelines, such as the USP and EU, provide comprehensive standards for evaluating impurities in pharmaceutical products.