The coupling of capillary electrophoresis (CE) to mass spectrometry (MS) with an electro-spray ionization (ESI) technique is generally performed for qualitative applications, and only few quantitative results have been reported. This paper investigates the validation of a CE-ESI-MS method for the analysis of a pharmaceutical formulation containing lidocaine. Some important ESI criteria are discussed including sheath-liquid composition, nebulizing gas pressure and position of the CE capillary outlet. After optimization of these parameters, an intermediate precision of about 5% was achieved. The latter, as well as efficiency and resolution, were compared to those achieved with UV detection. Besides, a multiple injection procedure was developed to reduce analysis time per sample and was successfully applied to both UV and MS detectors. The validation results achieved by multiple injections were identical to those obtained with classical injection, but afforded a gain of time by a factor of 2.5.