An advanced nuclear fuel cycle that aims to transmute the minor actinides (Am, Cm, Np) must include a separation of fission product lanthanides from the trivalent actinides. The TALSPEAK (Trivalent Actinide-Lanthanide Separation by Phosphorus reagent Extraction from Aqueous Komplexes) solvent extraction process provides an appropriate An3+/Ln3+ separation by matching the cation size-selective lanthanide extractant (bis-2-ethyl(hexyl) phosphoric acid, HDEHP) against the actinide-selective holdback reagent (diethylenetriamine-N,N,N’,N’’,N’’-pentaacetic acid, DTPA) in a concentrated lactic acid buffer. This study examines the impact of TALSPEAK reagents (extractant, holdback complexant, carboxylate buffer, pH) on the chemistry of a TALSPEAK separation based on extraction chromatographic (EXC) materials as an alternative to the lipophilic extractant system. The dual purpose is to evaluate the practical potential of this alternative and to gain deeper understanding of this chemistry. The effectiveness of alternative reagents, 2-ethyl(hexyl) phosphonic acid mono-2-ethyl(hexyl) ester (HEH[EHP]) (immobilized on a support) and triethylenetetramine-N,N,N’,N’’,N’’’,N’’’-hexaacetic acid (TTHA) (in the mobile phase) are also considered. Results indicate that the concentrated extractant in the EXC material behaves similarly to the lipophilic extractant system. It appears that lactate partitioning into the resin phase consumes resin capacity lowering extraction efficiency of the HDEHP EXC material, as is seen in conventional TALSPEAK-SX. The weaker hold-back reagent (under TALSPEAK aqueous conditions, pH ∼ 3.6), TTHA, actually provides slightly improved Am3+/Ln3+ separations performance relative to DTPA. The decreased sensitivity to pH and improved extraction efficiency that was reported by substituting HEH[EHP] for HDEHP in earlier studies of the solvent extraction system is confirmed by similar observations in extraction chromatography.