Abstract: | Inspired by the distinct chemical and physical properties of nanoparticles, here a novel open‐tubular capillary electrochromatography column was prepared by electrostatic assembly of poly(diallydimethylammonium chloride) onto the inner surface of a fused‐silica capillary, followed by self‐adsorption of negatively charged SH‐β‐cyclodextrin/gold nanoparticles. The formation of the SH‐β‐cyclodextrin/gold nanoparticles coated capillary was confirmed and characterized by scanning electron microscopy and energy dispersive spectrometry. The results of scanning electron microscopy and energy dispersive spectrometry studies indicated that SH‐β‐cyclodextrin/gold nanoparticles were successfully coated on the inner wall of the capillary column. The performance of the SH‐β‐cyclodextrin/gold nanoparticles coated capillary was validated by the analysis of six pairs of chiral drugs, namely zopiclone, carvedilol, salbutamol, terbutaline sulfate, phenoxybenzamine hydrochloride, and ibuprofen. Satisfactory enantioseparation results were achieved, confirming the use of gold nanoparticles as the support could enhance the phase ratio of the open‐tubular capillary column. Additionally, the stability and reproducibility of the SH‐β‐cyclodextrin/gold nanoparticles coated capillary column were also investigated. Then, this proposed method was well validated with good linearity (≥0.999), recovery (90.0–93.5%) and repeatability, and was successfully used for enantioseparation of ibuprofen in spiked plasma samples, which indicated the new column's potential usage in biological analysis. |