The fabrication and application of a novel multichannel amperometric detection system (MADS) with chemically modified microelectrodes (CMEs) for liquid chromatography (LC) are described. These CMEs are based on the immobilization of copper tetraaminophthalocyanine(CuTAPc) on platinum (Pt) microelectrodes by cyclic voltammetry (CV). The CMEs show good catalytic activity oxidation of several analytes including thiocompounds. With the multichannel amperometric detection system (MADS) coupled to LC, a three-dimensional hydrodynamic voltammogram (3D HDV) (i.e. current as a function of time and potential) is obtained. The optimum detection potentials of thiocompounds and other analytes at the CMEs are easy to find. The novel multichannel amperometric detector with CMEs shows good stability and reproducibility in detecting the thiocompounds and other analytes in LC. The linear ranges cover over three orders of magnitude and the limits of detection are 10 pmol for cysteine, 16 pmol for glutathione, 16 pmol for N-acetylcysteine, 10 pmol for ascorbic acid and 16 pmol for uric acid. The application of this method with microdialysis sampling and normal sampling in human whole blood assay is successful. The method of LC-MADS with microdialysis sampling is more useful to assay the compounds in the biological matrix.