Abstract: AimTo establish a sensitive and specific liquid chromatography-mass spectrometry (time-of-flight) ［LC-MS (TOF)］ method for the determination of donepezil in human plasma after an oral administration of 5 mg donepezil hydrochloride tablet. MethodsAlkalized plasma was extracted with isopropanol-n-hexane (3∶97) and loratadine was used as internal standard. Solutes were separated on a C₁₈ column with a mobile phase of methanol-acetate buffer (pH 4.0) (80∶20). Detection was performed on a time-of-flight mass spectrometry equipped with an ESI interface and operated in positive-ionization mode. Donepezil quantitation was realized by computing the peak area ratio (donepezil-loratadine) (donepezil m/z 380［M+H］⁺ and loratadine m/z 383［M+H］⁺) and comparing them with calibration curve (r=0.9998). ResultsThe linear calibration curve was obtained in the concentration range of 0.1-15 μg·L^-1. The detection limit of donepezil was 0.1 μg·L^-1. The average recovery was more than 90%. The intra-and inter-run precision was measured to be below 15% of RSD. ConclusionThe method is sensitive, simple and rapid, so, it can meet the need of the studies on the pharmacokinetics and bioavailability of donepezil.