Mercaptopropylsilica and silver nanoparticle (AgNP)-coated mercaptopropylsilica (Nucleosil 300, particle size 5 �m and pore size 10 nm) were prepared and their suitability as stationary phases for reversed-phase high-performance liquid chromatography (RP-HPLC) was evaluated. The retention mechanism was investigated for both ionogenic and non-ionogenic compounds using 150 x 4.6 mm i.d. columns, with emphasis on non-specific hydrophobic interactions and the possibility of specific hydrogen-bonding and donor-acceptor interactions between solutes and stationary phases. The retention of more than 40 substances including pyridines, anilines, phenols, benzoic acids and others was investigated. A different selectivity was obtained in the case of a series of anilines and pyridines. However, both phases showed a non-orthogonal retention mechanism, the latter being related to electron donor-acceptor interactions. The presence of hydrophilic interaction liquid chromatography (HILIC) retention behavior was demonstrated for mercaptopropylsilica phase.