Recycling minor actinides (Am, Cm and Np) from spent nuclear fuel is considered by a few countries as an important option for a future sustainable nuclear fuel cycle. For this purpose, solvent extraction processes are developed to separate minor actinides, especially from lanthanides and other fission products. The development of fast and powerful analytical methods is essential to acquire the data needed to model these processes and to improve their performances. For this purpose, this study presents the development, validation and application of a new analytical approach based on the simultaneous coupling of hydrophilic interaction chromatography (HILIC) to electrospray ionization mass spectrometry (ESIMS) and inductively coupled plasma mass spectrometry (ICPMS), using specific isotope dilution (SID) as a method of quantification for the determination of the affinity and selectivity of chelating molecules (TPAEN, NM and DTPA) towards lanthanides (Ln). The best separation conditions of natNd and natSm complexes formed with the three molecules were defined. Then, downscaling the separation was investigated, to reduce effluent volumes, the consumption of materials and the time devoted to experiments which are of concern in the nuclear field. The separation was carried out using an amide grafted stationary phase column in isocratic and gradient elution modes depending on the separation format. The separated complexes were online identified and the quantitative distribution of the Ln among the complexes was simultaneously determined owing to our quantification strategy. The results obtained were similar for the three separation formats, allowing us to validate the robustness of the method. By applying this method, the affinity of TPAEN, NM and DTPA present in competition for the complexation reaction with natNd and natSm was further determined in a single step, allowing a quick screening. Both selectivity and affinity of these molecules could be compared to select the most promising candidates. This approach can be advantageously extended to the evaluation of the affinity of various classes of chelating molecules used in very low quantities, towards elements of interest in the fields of energy, toxicology and the environment.