Solution stability and storage effect on selected metallodrugs: a multi-technique evaluation

Inorganic drugs have a huge impact in medicine, yet their solution behavior in presence of solvents for biological testing is often underestimated, even for clinically established agents. Speciation, hydrolysis, and redox processes can profoundly affect efficacy, safety, and reproducibility, with direct implications for both in vitro and in vivo testing. Here we present a proof-of-concept study highlighting the importance of systematic stability assessment prior to biological evaluation. Four representative metallodrugs were selected to capture diverse oxidation states, coordination geometries, and activation mechanisms: the ruthenium(III) complex NAMI-A, the platinum(II) drug oxaliplatin, the platinum(IV) derivative Hex-Pt, and the experimental gold(I) complex Npx-Au. Although limited in number, this panel demonstrates that meaningful insights can only be obtained through an integrated, multi-technique approach. By combining methods such as NMR spectroscopy, UV-Vis spectroscopy, and HPLC-MS, early degradation events can be reliably detected, optimal storage conditions defined, and misleading experimental outcomes avoided. Our findings emphasize that rigorous stability profiling over time is not optional but essential for accurate dosing, reproducibility, and correct interpretation of preclinical assays. This work establishes a framework for incorporating systematic solution stability evaluation into the development and experimental use of metallodrugs, ensuring more reliable translation from bench to clinic.