, Volume 66, Supplement 1, pp 31–36 | Cite as

Determination of Carbamazepine and its Main Metabolite Carbamazepine-10,11-Epoxide in Rat Brain Microdialysate and Blood Using ESI–LC–MS (Ion Trap)

  • E. Sener
  • O. T. Korkmaz
  • D. Yeniceli
  • D. Dogrukol-Ak
  • M. Tuncel
  • N. Tuncel


A new analytical method has been developed and validated for determination of the anti-epileptic drug carbamazepine (CBZ) and its main metabolite carbamazepine-10,11-epoxide (CBZ-E) using ESI–LC–MS (ion trap). The compounds were separated on a C18 (150 × 2.1 mm I.D., 3 μm particles) column and were isocratically eluted in the mobile phase consisting of water–acetonitrile–acetic acid (74.5:25:0.5, v/v) using the flow rate of 0.4 mL min−1. The other anti-epileptic drug oxcarbamazepine (OXC) was used as an internal standard. The retention times for CBZ-E, OXC and CBZ were 5.6, 6.8, 12.8 min. Signals of the compounds were monitored under multi-reaction monitoring mode (MRM) of ESI–LC–MS (ion trap) for the quantification. Selected ions of CBZ-E, OXC and CBZ in MRM were m/z 253→210, m/z 253→180 and m/z 237→194. The method was validated over the concentration range of 5.0–500.0 ng mL−1 and was applied to rat brain microdialysate and blood samples for the determination of CBZ and main metabolite. The brain microdialysate and the blood sample were collected simultaneously after intra-peritoneal injection of CBZ (12 mg kg−1) during a period of 10 h. No interference from endogenous substances and matrix effect were found on the separation of microdialysates and blood samples. The consequent signals of the compounds were resolved and integrated clearly. The LC–MS method was presented as an alternative to investigate pharmacokinetic parameters of CBZ and CBZ-E in blood and brain studies.


Column liquid chromatography–mass spectrometry ESI–LC–MS (ion trap) Brain microdialysate and blood sample Carbamazepine Carbamazepine-10,11-epoxide 



The authors acknowledge the instrumental support of Anadolu University Medicinal Plants and Medicine Research Center (AUBIBAM) and also acknowledge the excellent assistance of Mr. Ahmet Saraçoğlu and Ms. Nurcan Bektaş for in vivo experiments.


  1. 1.
    Mandrioli R, Albani F, Casamenti G, Sabbioni C, Raggi MA (2001) J Chromatogr B 762:109–116CrossRefGoogle Scholar
  2. 2.
    Scheyer RD, During MJ, Cramer JA, Toftness BR, Hochholzer JM, Mattson RH (1994) J Liq Chromatogr 17:1567–1577CrossRefGoogle Scholar
  3. 3.
    Graumlich JF, Mclaughlin RG, Birkhahn D, Shah N, Burk A, Jobe PC, Dailey JW (2000) Epilepsy Res 40:25–32CrossRefGoogle Scholar
  4. 4.
    Owen A, Tetty JN, Morgan P, Pirmohamed M, Park BK (2001) J Pharm Biomed Anal 26:573–577CrossRefGoogle Scholar
  5. 5.
    Reith DM, Cannell GR (1999) J Liq Chromatogr Rel Tech 22:1907–1918CrossRefGoogle Scholar
  6. 6.
    Dumortier G, Pons D, Zerrouk A, Januel D, Saba G, Degrassat K (2001) J Liq Chromatogr Rel Tech 24:3171–3180CrossRefGoogle Scholar
  7. 7.
    Hartter S, Jensen B, Hiemke C, Leal M, Weigmann H, Unger K (1998) J Chromatogr B 712:253–258CrossRefGoogle Scholar
  8. 8.
    Thormann W, Theurillat R, Wind M, Kuldvee R (2001) J Chromatogr A 924:429–437CrossRefGoogle Scholar
  9. 9.
    Kuldvee R, Thormann W (2001) Electrophoresis 22:1345–1355CrossRefGoogle Scholar
  10. 10.
    Kataoka Y, Makino K, Oishi R (1998) Electrophoresis 19:2856–2860CrossRefGoogle Scholar
  11. 11.
    Pucci V, Raggi MA (2005) Electrophoresis 26:767–782CrossRefGoogle Scholar
  12. 12.
    Casas MN, Blanco CC, Carretero AS, Gutiérrez AF (2004) Biomed Chromatogr 18:608–612CrossRefGoogle Scholar
  13. 13.
    Zhu Y, Chiang H, Radcliffe MW, Hilt R, Wong P, Kissinger CB, Kissinger PT (2005) J Pharm Biomed Anal 38:119–125Google Scholar
  14. 14.
    Heinig K, Henion J (1999) J Chromatogr B 732:445–458CrossRefGoogle Scholar
  15. 15.
    Xie F, Bruntlett CS, Zhu Y, Kissinger CB, Kissinger PT (2003) Anal Sci 19:479–485CrossRefGoogle Scholar
  16. 16.
    Tsai TH (2003) J Chromatogr B 797:161–173CrossRefGoogle Scholar
  17. 17.
    Lange ECM, de Boer AG, Breimer DD (2000) Adv Drug Deliv Rev 45:125–148CrossRefGoogle Scholar
  18. 18.
    Tunçel N, Şener E, Cerit C, Karasu U, Gürer F, Şahintürk V, Bayçu C, Ak D, Filiz Z (2005) Peptides 26:827–836CrossRefGoogle Scholar
  19. 19.
    Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates. Academic, New YorkGoogle Scholar
  20. 20.
    Trivedi RK, Kallem RR, Mullangi R, Srinivas NR (2005) J Pharm Biomed Anal 39:661–669CrossRefGoogle Scholar
  21. 21.
    Shah VP, Midha KK, Findlay WA, Hill HM, Hulse DJ, McGilveray IJ, Mc Key G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Pharm Res 17:1551–1557CrossRefGoogle Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlag/GWV Fachverlage GmbH 2007

Authors and Affiliations

  • E. Sener
    • 1
  • O. T. Korkmaz
    • 2
  • D. Yeniceli
    • 1
  • D. Dogrukol-Ak
    • 1
  • M. Tuncel
    • 1
  • N. Tuncel
    • 2
  1. 1.Faculty of Pharmacy, Department of Analytical ChemistryAnadolu UniversityEskisehirTurkey
  2. 2.Faculty of Medicine, Department of PhysiologyOsmangazi UniversityEskisehirTurkey

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