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Donepezil has been approved for the treatment of Alzheimer’s disease. In the present work, liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for donepezil quantification in rat plasma and brain samples were developed and validated. The analytes were separated on C18 column with mobile phase composed of methanol and ammonium acetate buffer (10mM, pH 5) (92:8, v/v) at a flow rate of 0.4 mL/min. The detection was in positive electrospray ionization mode (ESI +) and the m/z was 379,5>91,1 for donepezil. Quetiapine was used as the internal standard. The linearity ranges were of 5-250 ng/mL and 20-500 ng/g for plasma and brain samples, respectively. The method was fully validated in terms of linearity, accuracy, precision, matrix effect, carry-over effect and stability, according to the ANVISA, RDC no 27/2012. The precisions and accuracy were < 15%. The methods were successfully applied to plasma and brain pharmacokinetic studies in rats.
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