The basis for conducting bioequivalence studies is the determination of the bioavailability of the active substance of the drug at its place of action by establishing the concentration of the drug in biological fluids using sensitive analytical techniques. The bioanalytical technique used should provide reliable results which would lead to satisfactory level of interpretation. To investigate the bioequivalence of rivastigmine preparations, an 8 times more sensitive method (compared to the data in the available literature) for the quantitative determination of rivastigmine in human blood plasma by HPLC-MS/MS was developed. Rivastigmine is extracted from plasma by precipitation of plasma proteins with acetonitrile. Chromatographic separation of rivastigmine and the internal standard was carried out on a YMC Triart C18. 50×2.0 mm (1.9 µm) column in a gradient elution mode with a flow rate of 0.5 ml/min. A 0.1% solution of ammonium hydroxide and acetonitrile were used as mobile phases. The lower limit of the quantitative determination of the method was 25 pg/ml.