Cigarette smoke (CS) contains numerous compounds, among which free radicals and aldehydes that can potentially react with low molecular antioxidants, such as glutathione (GSH). Thus, the GSH depletion measurement can be used to assess the oxidative effect of the CS. The aims of this study were firstly, to develop a fast cell-free method to quantify the GSH depletion, secondly, to identify the GSH modifications. These measurements were carried out by putting in contact the CS (gas phase or whole smoke) with a GSH solution at a specific concentration. Afterward, an aliquot of this solution is analysed along the reference solution by capillary zone electrophoresis using UV detector (CZE) and Liquid chromatography with an electrochemical detection (LC-EC). CZE gives a fast quantification of GSH depletion allowing a fast screening of different cigarettes. In the other hand, LC-EC gives us specific information to quantitate and characterize the major specific products formed in direct reactions of CS (gas phase or whole smoke) components with GSH. Indeed, this method allows to detect GSH oxidative form (GSSG) or GSH adduct, such as GSH-aldehyde adducts.