[Determination of donepezil in human plasma by HPLC-MS]

To 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.

Alkalized 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).

The linear calibration curve was obtained in the concentration range of 0.1-15 micrograms.L-1. The detection limit of donepezil was 0.1 microgram.L-1. The average recovery was more than 90%. The intra- and inter-run precision was measured to be below 15% of RSD.

The method is sensitive, simple and rapid, so, it can meet the need of the studies on the pharmacokinetics and bioavailability of donepezil.