This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. The recommended
initial dose of donepezil is 5 mg taken once daily. Donepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations (Cmax) approximately 3–4 h S3I-201 purchase after dose administration. In humans, donepezil is metabolized mainly by the hepatic cytochrome P-450 2D6 and 3A4 isozymes. 2 Elimination of donepezil from the blood is characterized by a dose independent elimination half-life of about 70 h. 3 and 4 Because plasma donepezil concentrations are related linearly to acetylcholinesterase inhibition, 5 plasma donepezil concentration is a useful tool to predict donepezil efficacy. In the literature, methods have been reported for the quantification of donepezil in biological fluids. Methods are reported for the quantification of donepezil from biological
matrix using high-performance liquid chromatography (HPLC) equipped with an ultraviolet detector,2 and 3 fluorescence detector4 and mass spectrometric1, 6 and 7 detector. Methods are also reported for the quantification of enantiomers of donepezil from human plasma.8, 9 and 10 Other methods are reported with estimation of donepezil in plasma by capillary electrophoresis,11 hydrophilic interaction chromatography-tandem mass spectrometry,12 direct measurement,13 automated Florfenicol extraction.14 The HPLC methods used to determine donepezil in human plasma are insensitive because
of the lower limit of quantification (LOQ of >1.0 ng/ml). Some of the MAPK Inhibitor Library reported methods1, 4, 6, 10, 13 and 14 utilized analogue internal standards like diphenhydramine, lidocaine, pindolol, loratadine, escitalopram, etc. and are validated with different calibration curve ranges for the estimation of donepezil from rat plasma, human plasma and other biological fluids. Usage of labelled internal standards is recommended during the estimation of compounds from the biological matrices to minimize the matrix effects associated with the mass spectrometric detection. Bioequivalence and/or pharmacokinetic studies become an integral part of generic drug applications and a simple, sensitive, reproducible validated bioanalytical method should be used for the quantification of intended analyte. Bioequivalence studies for the donepezil needs to be performed with the dosage of 10 mg and 23 mg tablets to support the generic abbreviated new drug applications. For the pharmacokinetic and bioequivalence studies, quantification of donepezil was sufficient and quantification of its metabolites shall not be required. During the bioequivalence studies, appropriate lower limit of quantification needs to be used to appropriately characterize the concentration profile including the elimination phase.
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