“Bottom-up” LC approaches which have been employed to probe interactions between toxic metals and endogenous ligands. (a) The retention time of the toxic metal is measured as a function of the ligand concentration in the mobile phase, the pH, or the column temperature. (b) The retention time of the toxic metal/metalloid compound is measured as a function of an increasing concentration of Ligand 2 while leaving the concentration of Ligand 1 in the mobile phase constant. (c) The retention time of the metal-containing entity is measured as a function of an increased concentration of micelles in the mobile phase. Abbreviations: size exclusion chromatography (SEC), reversed-phase high performance liquid chromatography (RP-HPLC), mobile phase buffer (MP), L-glutathione (GSH), L-cysteine (Cys), and 2,3-dimercapto-1-propanesulfonic acid (DMPS).