Verapamil is commonly used for the treatments of supraventricular arrhythmias, angina and hypertension. The chemical structure and properties of Verapamil are stable and show no significant electrochemical activity without treating Verapamil with strong chemicals or high-energy radio-waves. This research develops a simple and effective method to oxidize Verapamil into electrochemical active derivatives with a novel ozone pre-treatment process. The oxidation reaction of Verapamil is investigated and confirmed with the UV-vis spectrometry and mass-spectrometry analyses. In order to further quantitatively evaluate the concentration of Verapamil, the oxidized Verapamil products are then detected using an electrochemical microchip with a gold nanoelectrode ensemble electrode (GNEE) as the working electrode. Enhanced by the excellent electrochemical catalytic properties of the GNEE working electrode, a significant redox peak is observed in the cyclic voltammetry test for the ozone treated Verapamil. Compared to the conventional analytical method of the UV absorption approach, the method developed greatly improves the sensitivity for detecting Verapamil without using complex pre-treatment process. The limit of detection for analyzing Verapamil with the method developed is 1.0 ng/mL, which is 125-fold lower than the reported serum concentration of 125.0 ng/mL. The experimental measured linear dynamic range is from 1.0 ng/mL to 100.0 mu g/mL with a correlation factor of 0.99. The development method provides a rapid and efficient way to quantitatively analyze Verapamil for clinical applications. (C) 2012 Elsevier Ltd. All rights reserved.