Document Detail

Quantitative determination of donepezil in human plasma by liquid chromatography/tandem mass spectrometry employing an automated liquid-liquid extraction based on 96-well format plates. Application to a bioequivalence study.
MedLine Citation:
PMID:  17113365     Owner:  NLM     Status:  MEDLINE    
An automated high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for quantitative determination of donepezil in human plasma. 150 MicroL of plasma samples were placed in 2.2 mL 96-deepwell plates and both donepezil and loratadine (IS) were extracted from human plasma by liquid-liquid extraction (LLE), using hexane as the organic solvent. Robotic liquid handling workstations were employed for all liquid transfer and solution preparation steps and resulted in a short sample preparation time. After vortexing, centrifugation and freezing, the supernatant organic solvent was evaporated and reconstituted in a small volume of reconstitution solution. The method developed, includes a sample analysis performed by reversed phase LC-MS/MS, with positive ion electrospray ionization, using multiple reaction monitoring (MRM). The chromatographic run time was set for 2.0 min with a flow rate of 0.7 mL/min in a C18 analytical column. The method was significantly sensitive, specific, accurate and precise for the determination of donepezil in human plasma and had the shortest run time. The curve was proven to be linear for the concentration range of 0.1-100 ng/mL. After validation, the method was applied to the rapid and reliable quantitative determination of donepezil in a bioequivalence study after per os administration of a 5mg donepezil tablet.
Constantinos Apostolou; Yannis Dotsikas; Constantinos Kousoulos; Yannis L Loukas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-17
Journal Detail:
Title:  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences     Volume:  848     ISSN:  1570-0232     ISO Abbreviation:  J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-27     Completed Date:  2007-06-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101139554     Medline TA:  J Chromatogr B Analyt Technol Biomed Life Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  239-44     Citation Subset:  IM    
Laboratory of Pharmaceutical Analysis and Bioequivalence Services (GLP Compliant), Department of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimioupoli Zografou, GR-157 71, Athens, Greece.
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MeSH Terms
Cholinesterase Inhibitors / administration & dosage,  blood,  pharmacokinetics
Chromatography, Liquid / instrumentation,  methods*
Indans / blood*,  chemistry,  pharmacokinetics
Molecular Structure
Piperidines / blood*,  chemistry,  pharmacokinetics
Reproducibility of Results
Tandem Mass Spectrometry / instrumentation,  methods*
Therapeutic Equivalency
Reg. No./Substance:
0/Cholinesterase Inhibitors; 0/Indans; 0/Piperidines; 120011-70-3/donepezil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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