Functionalized Metal Nanoparticles for Chromatographic Separation and Determination of Drugs and Biological Compounds

In recent years, the integration of functionalized metal nanoparticles (MNPs) into chromatographic systems has emerged as a promising and powerful strategy for improving the selectivity, sensitivity, and overall efficiency of separation processes involving pharmaceuticals and biologically active compounds. Owing to their exceptionally high surface-to-volume ratio, tunable surface chemistry, and unique electronic and optical properties, MNPs have demonstrated remarkable potential as both stationary phases and modifiers of conventional chromatographic adsorbents. Nanoparticles based on gold (AuNPs), silver (AgNPs), platinum (PtNPs, copper or copper oxide (CuNPs/CuONPs), and magnetic iron oxide (FeO) have shown enhanced chromatographic performance when incorporated into traditional matrices such as silica gel. A key aspect governing the performance of MNPs in chromatographic applications is surface functionalization, which enables the creation of nanomaterials with tailored physicochemical properties. These modifications provide tunable surface characteristics that directly influence the interaction mechanisms between the stationary phase and analytes, thereby enhancing separation selectivity. The surface functionalization process can occur through several mechanisms, most commonly covalent bonding, ionic interactions, and physical adsorption. In addition, more advanced strategies – such as encapsulation and dendronization – have recently gained increasing attention, offering improved stability and functional versatility. The selection of an appropriate functionalization method depends largely on the physicochemical properties of the nanoparticle core, the nature of the organic matrix, and the intended chromatographic application. This review summarizes the latest progress in the synthesis and functionalization of MNPs, discusses various immobilization strategies, and highlights their practical applications in the modern chromatographic separation of drugs and biological active compounds.