Single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) is a powerful approach for characterizing metallic nanoparticles (NPs) by size and concentration on a particle-by-particle basis [1]. However, this technique faces difficulties, such as the intrinsic matrix effect, which significantly impacts the results when analyzing real environmental and biological samples [2]. This effect is crucial for calculating SP-ICP-MS parameters like background signal, sensitivity, and transport efficiency, ultimately altering the final outcomes. To overcome these issues, high metrological quality analytical tools like isotope dilution analysis (IDA) can be employed to enhance signal discrimination in complex scenarios, even though its application is challenging and requires a thorough optimization process. Despite its potential, the combination of IDA with SP-ICP-MS has been scarcely utilized up to now, and it has been mainly focused on NP size characterization. However, incorporating recent advancements of SP-ICP-MS data acquisition and data treatment into this approach based on IDA would be advantageous to achieve reliable results both in terms of size and concentration.

Thus, this study explores the combination of IDA with SP-ICP-MS as an alternative to tackle the matrix effect in complex matrices for the determination of 30 and 50 nm platinum NPs (PtNPs), as a case study. Key considerations regarding the theoretical background and the implementation of this method for data acquisition with quadrupole instruments are discussed. The optimal tracer concentration for different PtNP sizes has been evaluated, resulting in 500 and 1,000 ng L-1 for 30 nm and 50 nm PtNPs, respectively, due to variations in the mean NP signal. Regarding data treatment, a valuable and practical in-house spreadsheet has been developed in this work, based on the application of the 5-sigma criterion for signal discrimination and the typical IDA equations. Additionally, the efficacy of this methodology in characterizing PtNPs in real samples has also been demonstrated with satisfactory results in terms of both sizing and counting. It is remarkable that our proposal extends the successful application of IDA-SP-ICP-MS to biological samples, such as cell culture media and human urine (eventually combined with tetramethylammonium hydroxide), for the first time, along with the previously investigated environmental samples, like synthetic and natural seawater.