A rapid and specific approach for direct measurement of donepezil concentration in human plasma by LC‐MS/MS employing solid‐phase extraction

A selective, rapid and simple liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method is described for assay of donepezil in human plasma using escitalopram as an internal standard. Chromatographic separation was achieved on a Betabasic‐C 8 , 5 µm, 100 × 4.6 mm column using methanol:water:formic acid (90:9.97:0.03, v/v/v) as mobile phase. Detection of donepezil and internal standard was achieved by ESI MS/MS in positive ion mode using 380.20/91.10 and 325.13/262.00 transitions, respectively. The linearity over the concentration range of 0.15–50 ng/mL for donepezil was obtained and the lower limit of quantification was 0.15 ng/mL. For each level of quality control samples, inter‐day and intra‐day precisions (RSD) were ≤8.92 and 10.35% and accuracy (%RE) were ≤7.33% and 9.33%, respectively. The recovery was more than 88.50% for both donepezil and internal standard by solid‐phase extraction, eliminating evaporation and reconstitution steps. Copyright © 2008 John Wiley & Sons, Ltd.