Silica gel particles are commonly used as a stationary phase in high-performance liquid chromatography (HPLC) for several reasons, including:
# High surface area: Silica gel particles have a high surface area, allowing direct interactions with solutes or after bonding of variety of ligands for versatile interactions with the sample molecules, leading to better separations.
# Chemical and thermal stability and inertness: Silica gel is chemically stable, as it usually does not react with either the solvents of the mobile phase nor the compounds being separated, resulting in accurate, repeatable and reliable analyses.
# Wide applicability: Silica gel is versatile and can be modified with various functional groups, making it suitable for a wide range of analytes and applications.
# Efficient separation: The unique properties of silica gel particles, combined with their high surface area and controlled average particle diameter pore size, facilitate efficient and precise separation of compounds in HPLC.
# Reproducibility: Silica gel particles can offer high batch-to-batch reproducibility, which is crucial for consistent and reliable HPLC analyses throughout decades.
# Particle diameter and pore size control: Silica gel can be engineered to have specific pore sizes, enabling precise control over separation based on molecular size.
# Cost-effectiveness: Silica is the most abundant element on earth, hence its gel is a cost-effective choice for HPLC applications, making it widely adopted in laboratories.
The United States Pharmacopoeia (USP) has classified HPLC columns by L# types. The most popular column in this classification is an octadecyl carbon chain (C18)-bonded silica (USP classification L1). This is followed by C8-bonded silica (L7), pure silica (L3), cyano-bonded silica (CN) (L10) and phenyl-bonded silica (L11). Note that C18, C8 and phenyl are dedicated reversed-phase stationary phases, while CN columns can be used in a reversed-phase mode depending on analyte and mobile phase conditions. Not all C18 columns have identical retention properties. Surface functionalization of silica can be performed in a monomeric or a polymeric reaction with different short-chain organosilanes used in a second step to cover remaining silanol groups (end-capping). While the overall retention mechanism remains the same, subtle differences in the surface chemistries of different stationary phases will lead to changes in selectivity.
Modern columns have different polarity depending on the ligand bonded to the stationary phase. PFP is pentafluorphenyl. CN is cyano. NH2 is amino. ODS is octadecyl or C18. ODCN is a mixed mode column consisting of C18 and nitrile. 
Recent developments in chromatographic supports and instrumentation for liquid chromatography (LC) facilitate rapid and highly efficient separations, using various stationary phases geometries. Various analytical strategies have been proposed, such as the use of silica-based monolithic supports, elevated mobile phase temperatures, and columns packed with sub-3 μm superficially porous particles (fused or solid core) or with sub-2 μm fully porous particles for use in ultra-high-pressure LC systems (UHPLC).