We analyzed the performance and throughput of currently available analytical techniques for quantifying body burden and cell internalization/distribution of silver nanoparticles (Ag NPs). Our review of Ag NP biological fate data shows that most of the evidence gathered for Ag NPs body burden actually points to total Ag and not only Ag NPs. On the other hand, Ag NPs were found inside the cells and tissues of some organisms, but comprehensive explanation of the mechanism(s) of NP entry and/or in situ formation is usually lacking. In many cases, the methods used to detect NPs inside the cells could not discriminate between ions and particles. There is currently no single technique that would discriminate between the metals species, and at the same time enable localization and quantification of NPs down to the cellular level. This paper serves as an orientation towards selection of the appropriate method for studying the fate of Ag NPs in line with their properties and the specific question to be addressed in the study. Guidance is given for method selection for quantification of NP uptake, biodistribution, precise tissue and cell localization, bioaccumulation, food chain transfer and modeling studies regarding the optimum combination of methods and key factors to consider.
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