In this work, a simple method based on reverse-phase high-performance liquid chromatography (HPLC) with tris(2,2-bipyridyl)ruthenium(II) [Ru(bpy)32+]-modified single Pt wire electrogenerated chemiluminescence (ECL) detector for the determination of three antiemetic drugs was developed. The proposed detector was based on Ru(bpy)32+ immobilized on a Pt wire surface with Nepem-105D ion exchange solution. The method allows for the simultaneous detection of these antiemetic drugs in human serum and offers short analysis times. In this HPLC-ECL system, luminescence reagent Ru(bpy)32+ was immobilized, thus, no Ru(bpy)32+ delivery system is needed, furthermore, stable ECL response of analytes can obtained. Besides conserving the expensive reagent, the experimental setup is also simplified.