Radium Speciation in Simulated Digestive Biofluids: Insights from Electrospray Ionization Mass Spectrometry and Thermodynamic Modeling

Radium (Ra) poses a potential radiotoxic hazard when accidentally ingested, even at moderate amounts. However, its molecular behavior in the human digestive system has remained largely unexplored. Here, we present the first direct characterization of Ra speciation in synthetic gastrointestinal biofluids, combining electrospray ionization mass spectrometry (ESI‐MS) with thermodynamic modeling in PHREEQC, with barium (Ba) also investigated as a homolog. In both experimental and modeled biofluid systems, the free Ra 2+ and Ba 2+ ions were the dominating species in solution, indicating theoretical availability for absorption in the small intestine. Efficacy of classical complexing agents such as EDTA for Ra in the biofluids is minimal, while more selective ligands such as 18‐crown‐6 readily form complexes. Sorption to digestive proteins is negligible, and precipitation at investigated concentrations suggest that not all the ingested Ra and Ba are bioavailable. Simulated oral uptake studies using brazil nuts naturally containing elevated Ra concentrations demonstrate that only a small fraction of Ba is leached, and no organic barium complexes are detected. Together, these findings provide the first direct insights into Ra speciation in digestive biofluids, offering a framework for improved risk assessment of radionuclide ingestion and development of potential decorporation strategies.