, Volume 75, Issue 15–16, pp 857–866 | Cite as

LC–MS–MS Method for the Simultaneous Determination of Donepezil Enantiomers in Plasma

  • Adriana Iordachescu
  • Luigi Silvestro
  • Ariana Tudoroniu
  • Simona Rizea Savu
  • Valentin Ciuca


This paper presents a new analytical method with adequate sensitivity, precision, accuracy, and specificity to quantitatively determine (−)-donepezil and (+)-donepezil in plasma, at concentrations that can be expected in real samples of pharmacokinetic studies. This method combines a HPLC separation on cellulose tris (3,5-dimethylphenyl carbamate) coated on 5-μm silica-gel column known as CHIRALCEL OD–RH eluted with mobile phase consisting of acetonitrile and ammonium bicarbonate and MS–MS detection. Under the HPLC conditions used (−)-donepezil and (+)-donepezil, as well as the enantiomers of the internal standard d7-donepezil, eluted at 5 and 6.25 min, respectively. The curve fittings were optimal for the entire calibration range (0.05–25.0 ng mL−1) with correlation coefficients (r) = 0.999 for (−)-donepezil and (r) = 0.999 for (+)-donepezil (linear regression model with 1/x2 weighing). The assay method showed a good specificity for donepezil enantiomers, and it could be successfully applied to pharmacokinetic studies.


LC–MS–MS HPLC Donepezil Enantiomers Pharmacokinetic Chiral stationary phase 


  1. 1.
    Gauthier S, Panisset M, Nalbantoglu J, Poirier J (1997) Can Med Assoc J 157:1047–1052Google Scholar
  2. 2.
    Sugimoto H, Yamanishi Y, Iimura Y, Kawakami Y (2000) Curr Med Chem 7(3):303–339Google Scholar
  3. 3.
    Sugimoto H, Ogura H, Arai Y, Iimura Y, Yamanishi Y (2002) Jpn J Pharmacol 89:7–20CrossRefGoogle Scholar
  4. 4.
    Budhavari S (2001) Merck Index, 13th edn. Merck and Co. Inc. Whitehouse Station, 3453Google Scholar
  5. 5.
    Radwan MA, Abdine HH, Al-Quadeb BT, Aboul-Enein HY, Nakashima K (2006) J Chromatogr B Analyt Technol Biomed Life Sci 830(1):114–119CrossRefGoogle Scholar
  6. 6.
    Eeckhaut AV, Michotte Y (2010) Pharmacological importance of chiral separations, chiral separations by capillary electrophoresis. Chromatographic science series, vol 100. CRC Press, Boca RatonGoogle Scholar
  7. 7.
    Haginaka J, Seyama C (1992) J Chromatogr 577(1):95–102CrossRefGoogle Scholar
  8. 8.
    Matsui K, Oda Y, Nakata H, Yoshimura T (1999) J Chromatogr B Biomed Sci Appl 729(1–2):147–155CrossRefGoogle Scholar
  9. 9.
    Abbas S, Fayez Y, Fattah A (2006) Chem Pharm Bull 54(10):1447–1450CrossRefGoogle Scholar
  10. 10.
    EMA-Guideline on the investigation of bioequivalence, Londra (2010)
  11. 11.
    Food and Drug Administration (May 2001) Guidance for Industry 436/Bioanalytical method validationGoogle Scholar
  12. 12.
    Tiseo PJ, Perdomo CA, Friedhoff LT (1998) Br J Clin Pharmacol 46:40–44CrossRefGoogle Scholar
  13. 13.
    Viswanathan CT, Bansal S, Booth B, DeStefano AJ, Rose MJ, Sailstad J, PShah VP, Skelly JP, Swann PG, Weiner R (2007) Pharma Res 24(10):1962–1973Google Scholar
  14. 14.
    Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Anal Chem 75:3019–3030CrossRefGoogle Scholar
  15. 15.
    Kelly T, Gray TR, Huestis MA (2008) J Chromatrogr B Biomed Sci Appl 867(2):194–204CrossRefGoogle Scholar
  16. 16.
    Nguyen LA, He H, Pham-Huy C (2006) IJBS 2:85–100Google Scholar
  17. 17.
    Berthod A (2010) Chiral recognition in separation methods. Mechanisms and applications. Springer, BerlinCrossRefGoogle Scholar
  18. 18.
    Gübitz G, Schmid MG (2004) Chiral separation principles, chiral separations methods and protocols, methods in molecular biology. Humana Press, New JerseyGoogle Scholar
  19. 19.
    Beesley TE, Scott RPW (1998) Chiral chromatography. Separation science series, Wiley, New YorkGoogle Scholar
  20. 20.
    Tiseo PJ, Rogers SL, Friedhoff LT (1998) Br J Clin Pharmacol 46:13–18CrossRefGoogle Scholar
  21. 21.
    Rogers SL, Friedhoff LT (1998) Br J Clin Pharmacol 46:1–6CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Adriana Iordachescu
    • 1
    • 2
  • Luigi Silvestro
    • 3
  • Ariana Tudoroniu
    • 1
  • Simona Rizea Savu
    • 3
  • Valentin Ciuca
    • 1
  1. 1.Pharma Serv Int’l SRLBucharestRomania
  2. 2.Department of Analytical Chemistry, Faculty of ChemistryUniversity of BucharestBucharestRomania
  3. 3.3S-Pharmacological Consultation and Research GmbHHarpstedtGermany

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