Development of a capillary electrophoresis-mass spectrometry method for the determination of rivastigmine in human plasma--optimization of the limits of detection and quantitation

A capillary zone electrophoresis-electrospray ionization-mass spectrometry (CZE-ESI-MS) method was developed for the analysis of the acetylcholinesterase inhibitor rivastigmine. Several electrophoretic and ESI-MS parameters were investigated in order to improve sensitivity. These parameters were categorized in three areas: (i) background electrolyte (BGE) parameters, (ii) sheath liquid parameters, and (iii) spray chamber parameters. The optimized results were obtained by using 40-mM ammonium acetate at pH 9 as BGE, a sheath liquid of 1% acetic acid in water:MeOH (50:50 v/v) at a flow rate of 10 μL/min, and a drying gas flow rate that was set at 6 L/min and at a temperature of 200°C. These parameters provided limit of detection and limit of quantitation of 2.8 ng/mL and 8.4 ng/mL, respectively. The optimal CZE-ESI-MS conditions were applied to a plasma sample obtained from an Alzheimer's disease patient following rivastigmine patch administration, and the mean (±standard deviation) plasma concentration was estimated to be 14.6 (±1.7) ng/mL. Several sample preparation procedures were examined, and solid-phase extraction using a C18 cartridge proved to be the most effective procedure, since higher sensitivity and recovery were obtained. In addition, precision was evaluated based on migration time and peak area in plasma, and the relative standard deviations were in the range of 0.10-0.16% and 0.62-9.0%, respectively.