Determination of donepezil hydrochloride in human and rat plasma, blood and brain microdialysates by HPLC with a short C sub(30) column

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 41; no. 1; pp. 201 - 206
• Main Authors: Nakashima, Kenichiro, Itoh, Keiko, Kono, Michio, Nakashima, Mihoko N, Wada, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: 01-01-2006
• ISSN: 0731-7085
• DOI: 10.1016/j.jpba.2005.10.017

A simple and sensitive HPLC method with fluorescence (FL) detection for determination of donepezil (DP) in plasma and microdialysate samples was developed. A rapid isocratic separation of DP could be achieved by a short C sub(30) column using mobile phases of 25 mM citric acid/50 mM Na sub(2)HPO sub(4) (pH 6.0)-CH sub(3)CN (73:27%, v/v) containing 3.5 mM sodium 1-octanesulfonate for plasma and H sub(2)O-CH sub(3)CN-CH sub(3)OH (80:17:3%, v/v/v) containing 0.01% acetic acid for microdialysate. The eluate was monitored at 390 nm with an excitation at 325 nm. The detection limits (S/N = 3) of DP for human plasma, rat plasma and rat brain or blood microdialysates were 0.2, 1.0 and 2.1 ng/ml, respectively. Reproducible results could be obtained by using (+/-)-2-[(1-benzyl-piperidine-4- yl)ethyl]-5,6-dimethoxyindan-1-one hydrochloride as an internal standard (IS). The method was successfully applied for monitoring of DP levels in rat plasma, blood and brain microdialysates and patient plasma.