Evaluation of elemental impurities and particle size distribution in nanomedicine using asymmetric flow field-flow fractionation hyphenated to inductively coupled plasma mass spectrometry

Nanomedicines, which consist of nanoparticles as active ingredients, have been developed and approved for pharmaceutical use. However, no method has been established to quantify ions and nanoparticles containing the same elements separately. We developed an asymmetric flow field-flow fractionation hyphenated to inductively coupled plasma mass spectrometry (AF4-ICP-MS) to assess elemental impurities from ions and nanoparticles of different sizes. Our method effectively removed silicon (Si) ions from a mixture of Si ions and silica nanoparticles. For iron (Fe), we observed that 28.5 % of Fe ions were converted into insoluble hydroxide colloids in a diluted solution at neutral pH. Nevertheless, we could separate Fe ions from iron oxide nanoparticles and iron hydroxide colloids converted from Fe ions. We applied this method to Resovist®, a nanomedicine composed of carboxydextran-coated iron oxide nanoparticles, and found that 0.022 % of Fe was present in ionic form. The particle size of Resovist® was also evaluated using AF4-ICP-MS, which applies to nano-to submicron-size particles. The active ingredient in Resovist® had a particle size smaller than 30 nm, and some aggregated particles exhibited a hydrodynamic diameter of approximately 50 nm. Our findings indicate that AF4-ICP-MS can evaluate the physicochemical properties of nanomedicines, which are essential for their quality, efficacy, and toxicity.