title: Rapid and sensitive determination of donepezil in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.
abstract: A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of donepezil in human plasma samples. Diphenhydramine was used as the internal standard. The collision-induced transition m/z 380 --> 91 was used to analyze donepezil in selected reaction monitoring mode. The signal intensity of the m/z 380 --> 91 transition was found to relate linearly with donepezil concentrations in plasma from 0.1-20.0 ng/mL. The lower limit of quantification of the LC/MS/MS method was 0.1 ng/mL. The intra- and inter-day precisions were below 10.2% and the accuracy was between -2.3% and +2.8%. The validated LC/MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 5 mg donepezil hydrochloride. The non-compartmental pharmacokinetic model was used to fit the donepezil plasma concentration-time curve. Maximum plasma concentration was 12.3 +/- 2.73 ng/mL which occurred at 3.50 +/- 1.61 h post-dosing. The apparent elimination half-life and the area under the curve were, respectively, 60.86 +/- 12.05 h and 609.3 +/- 122.2 ng . h/mL. LC/MS/MS is a rapid, sensitive and specific method for determining donepezil in human plasma samples.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xie
authors.forename: Qiongfeng
authors.initials: Q
authors.lastname: Liao
authors.forename: Xinjun
authors.initials: X
authors.lastname: Xu
authors.forename: Meicun
authors.initials: M
authors.lastname: Yao
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Wan
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D003198:Computer Simulation; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013997:Time Factors
chemical_list: D007189:Indans; D010880:Piperidines; D000077265:Donepezil