Elemental impurities analysis

Profound regulatory changes mean that the consideration of elemental impurities will be mandatory for all pharmaceutical products as of January 2018.

Since elemental impurities constitute not only a toxicological risk for the patient but also may affect the quality and efficacy of pharmaceutical products, their analysis plays an important role within the development and quality control of pharmaceuticals.

So far heavy metal analysis was performed by sulfidic precipitation according to a limit test stated in USP chapter <231> and Ph. Eur. 2.4.8. This more than 100 years old procedure is nonspecific and does not allow the determination of concrete quantitative results.

Finally, after an intensive period of development the outdated wet chemical analysis is being replaced step by step by modern instrumental analysis in all relevant regulations.

Due to these changes the use of ICP-OES or ICP-MS together with reliable sample preparation techniques such as microwave-assisted closed vessel digestion is going to become the future imperative for the specific quantification of elemental impurities.

Anton Paar conducted an experiment in order to demonstrate the excellent suitability of their instruments for sample preparation relating to elemental impurities analysis.

Three pharmaceutical products were analyzed: Painkilling Tablet, Dietary Supplement Capsule and Cold Syrup.

According to USP <233> the samples were spiked between 50 and 150 % of the target limit of each element. For evaluating these limits the respective PDE and the maximum daily dose stated on the package leaflet of the product were taken into consideration. The performance of the digestion was evaluated by calculating the recovery rates of the measured samples in relation to the theoretical values (unspiked sample + spiked value).

The focus was set on the "big four", Cd, Pb, As and Hg, since they have the lowest PDE levels. Particularly As and Hg compounds are analytically demanding due to their volatile behaviour.