LC–MS–MS Method for the Simultaneous Determination of Donepezil Enantiomers in Plasma

Abstract

This paper presents a new analytical method with adequate sensitivity, precision, accuracy, and specificity to quantitatively determine (−)-donepezil and (+)-donepezil in plasma, at concentrations that can be expected in real samples of pharmacokinetic studies. This method combines a HPLC separation on cellulose tris (3,5-dimethylphenyl carbamate) coated on 5-μm silica-gel column known as CHIRALCEL OD–RH eluted with mobile phase consisting of acetonitrile and ammonium bicarbonate and MS–MS detection. Under the HPLC conditions used (−)-donepezil and (+)-donepezil, as well as the enantiomers of the internal standard d7-donepezil, eluted at 5 and 6.25 min, respectively. The curve fittings were optimal for the entire calibration range (0.05–25.0 ng mL−1) with correlation coefficients (r) = 0.999 for (−)-donepezil and (r) = 0.999 for (+)-donepezil (linear regression model with 1/x2 weighing). The assay method showed a good specificity for donepezil enantiomers, and it could be successfully applied to pharmacokinetic studies.