, Volume 60, Supplement 1, pp S245–S251 | Cite as

Chiral Characterization and Quantification of Deprenyl-N-oxide and Other Deprenyl Metabolites in Rat Urine by Capillary Electrophoresis

  • É.  Szöko
  • T. Tábi
  • A. S. Halász
  • M. Pálfi
  • H. Kalász
  • K. Magyar


Chiral capillary electrophoresis has been validated for the quantitative analysis of R-(-)-deprenyl (selegiline) and seven of its metabolites, among them the diastereomeric pair of selegiline-N-oxide in rat urine. Linear calibration curves were obtained over the concentration range: 0.5–100 μM for selegiline, N-desmethylselegiline, methamphetamine, amphetamine, and selegiline-N-oxides, and from 0.1-100 μM for para-hydroxylated derivatives of N-desmethylselegiline, methamphetamine, and amphetamine. The inter and intra-assay precision and accuracy varied by <15% for all analytes at concentrations of 2.5, 10 and 25 μM, and <20% at the lower limit of quantification (0.5 or 0.1 μM). The sample extraction procedure was optimised, and sample recoveries ranged: 80–111% and 74–91% at concentrations of 1 and 10 μM, respectively. The extracted urine samples retained quantitative accuracy for at least 5 days after storage at 4 °C. The validated method was used for in vivo metabolism studies in rats treated with either single or repeated dose of selegiline, or selegiline-N-oxide. Stereoselective N-oxidation of selegiline and rapid urinary excretion of selegiline-N-oxides have been observed. The most abundant metabolites of selegiline were the desalkylated and para-hydoxylated derivatives excreted in both conjugated and unconjugated forms in rat urine.


Capillary electrophoresis Method validation In vivo metabolism Deprenyl and deprenyl-N-oxide 


  1. Magyar K, Vizi ES, Ecseri Z, Knoll J (1967) Acta Physiol Hung 32:377–387Google Scholar
  2. Magyar K, Haberle D (1999) Neurobiology 7:175–190PubMedGoogle Scholar
  3. Ebadi M, Sharma S, Shavali S, Refaey H (2002) J Neurosci Res 67:285–289CrossRefPubMedGoogle Scholar
  4. Tatton WG, Chalmers-Redman RM, Tatton N (2003) J Neural Transm 110:509–515CrossRefPubMedGoogle Scholar
  5. Tatton WG, Chalmers-Redman RM (1996) Neurology 47S3:171–183Google Scholar
  6. Reynolds GP, Elsworth JD, Blau K, Sandler M, Lees AJ, Stern GM (1978) Br J Clin Pharmacol 6:542–544PubMedGoogle Scholar
  7. Heinonen EH, Myllyla V, Sotaniemi K, Lammintausta R, Salonen JS, Anttila M, Savijarvi M, Kottila M, Rinne UK (1989) Acta Neurol Scand 126:93–99Google Scholar
  8. Shin H-S (1997) Drug Metab Disp 25:657–662Google Scholar
  9. Magyar K, Tóthfalusi L (1984) Pol J Pharmacol Pharm 36:373–384PubMedGoogle Scholar
  10. Yoshida T, Yamada Y, Yamamoto T, Kuroiwa Y (1986) Xenobiotica 16:129–136PubMedGoogle Scholar
  11. Szoko É, Magyar K (1996) Int’l J Pharm Adv 1:320–327Google Scholar
  12. Lengyel J, Magyar K, Hollósi I, Bartók T, Báthori M, Kalász H, Fürst Z (1997) J Chromatogr A 762:321–326CrossRefPubMedGoogle Scholar
  13. Kalász H, Kerecsen L, Knoll J, Pucsok J (1990) J Chromatogr, 499:589–599Google Scholar
  14. Wu RF, Ichikawa Y (1995) FEBS Lett 358:145–148CrossRefPubMedGoogle Scholar
  15. Katagi M, Tatsuno M, Miki A, Nishikawa M, Nakajima K, Tsuchihashi H (2001) J Chromatogr B 759:125–133CrossRefGoogle Scholar
  16. Katagi M, Tatsuno M, Tatsuno H, Miki A, Kamata T, Nishioka H, Nakajima K, Nishikawa M, Tsuchihashi H (2002) Xenobiotica 9:823–831CrossRefGoogle Scholar
  17. Tábi T, Magyar K, Szöko É (2003) Electrophoresis 24:2665–2673CrossRefPubMedGoogle Scholar
  18. Szebeni G, Lengyel J, Szekacs G, Magyar K, Gaal J, Szatmári I (1995) Acta Physiol Hung 83:135–141PubMedGoogle Scholar
  19. Haberle D, Kalász H, Hollósi I, Pucsok J, Csermely T, Magyar K, Tóth-Molnár E, Chromatographia (1999) 50:415–422Google Scholar
  20. Kikura R, Nakahara Y, Kojima S (2000) J Chromatogr B 741:163–173CrossRefGoogle Scholar
  21. Slawson MH, Taccogno JL, Foltz RL, Moody DE (2002) J Anal Toxicol 26:430–437PubMedGoogle Scholar
  22. Kim E-M, Chung H-S, Lee K-J, Kim H-J (2000) J Anal Toxicol 24:238–244PubMedGoogle Scholar
  23. Schachter M, Marsden C D, Parkes JD, Jenner P, Testa B (1980) J Neurol Neurosurg Psychiatry 43:1016–1021PubMedGoogle Scholar
  24. Szöko É, Kalász H, Magyar K (1999) Eur J Drug Metab Pharmacokinet 24:315–319PubMedGoogle Scholar
  25. Laine K, Anttila M, Huupponen R, Maki-Ikola O, Heinonen E (2000) Clin Neuropharmacol 23:22–27CrossRefPubMedGoogle Scholar
  26. Clement B, Behrens D, Möller W, Cashman JR (2000) Chem Res Toxicol 13:1037–1045CrossRefPubMedGoogle Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 2004

Authors and Affiliations

  • É.  Szöko
    • 1
  • T. Tábi
    • 1
  • A. S. Halász
    • 1
  • M. Pálfi
    • 1
  • H. Kalász
    • 2
  • K. Magyar
    • 1
    • 3
  1. 1.Department of PharmacodynamicsSemmelweis UniversityBudapestHungary
  2. 2.Department of Pharmacology and PharmacotherapySemmelweis UniversityBudapestHungary
  3. 3.Neurochemical Research Unit of the Hungarian Academy of SciencesBudapestHungary

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