Metrological advances for inorganic engineered nanomaterials have been mainly driven by industrial needs to produce more effective and safer products as well as comply with emerging regulation (1,2). In this vein, The EU definition of NM (2011/696/EU, revised in June 2022) for regulatory purposes points to the determination of number concentration as a key requirement. With regards to plastics, two-thirds of the 359 million tonnes of plastic produced annually at the global scale is released into the environment, where it undergoes complex physicochemical processes, fragmenting into small microplastics (SMPs). However, the potential risks from exposure to SMPs in humans are yet to be fully understood. In this context, accurate information regarding number-based concentration for small microplastics (1-10 µm) is needed for future comprehensive risk assessments. Finally, the European Medical Agency (EMA) roadmap to 2025 has stated the need to develop and standardise new testing methods related to the quality and safety assessment of nanomedicines (e.g. lipid-based delivery systems) with focus on establishing the relationship between critical quality attributes and biological activity.

Although advances in the accurate determination of particle number concentration have been reported, remaining challenges include its accurate determination for particles with size in the few nm range present in matrices of high complexity as well as the lack of certified reference materials for method validation. For lipid-based delivery systems, Metrology is still in its infancy with the emerging requirement of having validated methods to accurately measure physicochemical properties (e.g. size, size distribution, surface chemistry, concentration, lipid composition) as well as drug loading, stability and characterize new reference materials.

This lecture will illustrate how some of those challenges have been overcome through a variety of practical examples in which ICP-MS platforms supported by other techniques play a key role (3,4). It will also highlight remaining analytical challenges driven by legislation, existing reference materials as well as the importance of interlaboratory comparisons to assess the state-of-the-art of measurements performed by expert laboratories.

References
1. Cosmetics Regulation EC 1223/2009
2. Food and Feed Regulation EC 178/2002
3. D. Bartczak, S. Nunez, M. Palmai, S. Hill, P. Petrov, Z, Varga, R. Szalay and H. Goenaga-Infante, Anal. Chem., 2024, https://doi.org/10.1021/acs.analchem.4c00021
4. D. Ojeda, D. Bartczak, M. Singh, P. Hancok and H. Goenaga-Infante. J. Anal. At. Spectrom., 2024, DOI https://doi.org/10.1039/D4JA00074A

Dr. Heidi Goenaga-Infante