J Appl Biomed 1:99-106, 2003 | DOI: 10.32725/jab.2003.015

Capillary electrophoresis determination of huperzine A: A new prospective anti-dementia drug

Eladia M. Peña-Méndez1,3, Tomáš Hottmar1, Josef Havel1, Jiří Patočka2,*
1 Department of Analytical Chemistry, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic
2 Military Medical Academy, Department of Toxicology, 502 60 Hradec Králové and Department of Radiology, Faculty of Health and Social Care, University of South Bohemia, České Budějovice, Czech Republic
3 On leave from: Department of Analytical Chemistry, Nutrition and Food Science, University of La Laguna, 38071 La Laguna, Tenerife, Spain

Huperzine A is an alkaloid isolated from the Chinese plant Huperzia serrata. The absorption spectra and electrophoretic behaviour of the compound were studied. The compound shows two absorption maxima (λmax 230 and 310nm). The protonation constant was determined by spectrophotometry and capillary zone electrophoresis (CZE) and the recommended value is pK=7.70±0.07. A CZE method for the determination of Huperzine A in pharmaceutical tablets and serum has been developed. The method is based on separation of the compound as a protonated species with electrophoretic mobility determined as 50.7 x 10-9 m2V-1s-1. The optimal separation conditions were: acetate buffer (pH 4.60; 20 mM) as a background electrolyte, separation voltage 20 kV, temperature 25 °C, hydrodynamic injection 10 s and detection at wavelengths 230 and 310 nm. The analyses were run in an uncoated fused-silica capillary with total length of 47.5 cm (39.0 cm to the detector) and 75 μm I.D. The detection limit was found to be 70 μg/l. The method of Huperzine A determination was applied for analysis of various pharmaceutical products. The results were found to be in good agreement with the declared amount. The precision of the method is ±2.30%. A method for the determination of HupA in serum was also developed with detection limit ≈ 110 μg/l, which is applicable for pharmacokinetics and therapeutic drug monitoring of this compound.

Keywords: huperzine A; Alzheimer's disease; capillary zone electrophoresis

Received: September 10, 2002; Published: July 31, 2003  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Peña-Méndez EM, Hottmar T, Havel J, Patočka J. Capillary electrophoresis determination of huperzine A: A new prospective anti-dementia drug. J Appl Biomed. 2003;1(2):99-106. doi: 10.32725/jab.2003.015.
Download citation

References

  1. Ashani Y., J. Grunwald, C. Kronman, B. Velann, A. Shafferman: Role of tyrosine 337 in the binding of huperzine A to the active site of human acetylcholinesterase. Mol. Pharmacol. 45: 555-560, 1994.
  2. Bai D.L., X..C. Tang, X.C. He: Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Curr. Med. Chem. 7: 355-374, 2000. Go to original source... Go to PubMed...
  3. Cheng D.H., H. Ren, C.C. Tang: Huperzine A, a novel promising acetylcholinesterase inhibitor. Neuroreport 8: 97-101, 1996. Go to original source... Go to PubMed...
  4. Cummings J.L. and G. Cole: Alzheimer disease. J. Am.. Med. Assoc. 287: 2335-2338, 2002. Go to original source... Go to PubMed...
  5. Emre M.: Switching cholinesterase inhibitors in patients with Alzheimer's disease. Int. J. Clin. Pract., Suppl. 127: 64-72, 2002.
  6. Grunwald J., L. Raveh, B.P. Doctor, Y. Sahani: Huperzine A as a pretreatment candidate drug against nerve agent toxicity. Life Sci. 54: 991-997, 1994. Go to original source... Go to PubMed...
  7. Havel J. and J. Jánoš: Evaluation of capillary zone electrophoresis equilibrium data using the CELET program. J. Chromatogr A 786: 321-331, 1997. Go to original source...
  8. Kukull W.A. and J. D. Bowen: Dementia epidemiology. Med. Clin. North Am. 86: 573-590, 2002. Go to original source... Go to PubMed...
  9. Lallement G., V. Baille, D. Baubichon, P. Carpentier, J.M. Collombet, P. Filliat, A. Foquin, E. Four, C. Masqueliez, G. Testylier, L. Tonduli, F. Dorandeu: Review of the value of huperzine as pretreatment of organophosphate poisoning. Neurotoxicology 23: 1-5, 2002. Go to original source... Go to PubMed...
  10. Lawrence A.D. and B. J. Sahakian: The cognitive psychopharmacology of Alzheimer's disease: focus on cholinergic systems. Neurochem. Res. 23: 787-794, 1998. Go to original source... Go to PubMed...
  11. Leggett D.J. (ed.): Computational Methods for Determination of Formation Constants, Plenum Press, New York, 1985. Go to original source...
  12. Malovaná S., D. Gajdošová, J. Benedík, J. Havel: Determination of esmolol in serum by capillary zone electrophoresis and its monitoring in course of heart surgery. J. Chromatogr. B, 760: 37-43, 2001. Go to original source...
  13. Mazurek A.A.: Treatment of Alzheimer's disease. N. Engl. J. Med. 342: 821, 2000. Go to original source...
  14. McKinney M., J.H. Miller, F. Yamada, W. Tuckmantel, A.P.: Kozikowski Potencies and stereoselectivities of enantiomers of huperzine A for inhibition of rat cortical acetylcholinesterase. Eur. J. Pharmacol. 203: 303-305, 1991. Go to original source... Go to PubMed...
  15. Patočka J.: Může stará čínská droga pomoci pacientům s Alzheimerovou chorobou? Psychiatrie 3: 23-24, 1999.
  16. Poirier J.: Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. Int. J. Clin. Pract., Suppl. 127: 6-19, 2002.
  17. Qian B.C., M. Wang, Z.F. Zhou, K. Chen, R.R. Zhou, G.S. Chen: Pharmacokinetics of tablet huperzine A in six volunteers. Acta Pharmacolog. Sinica 16: 396-398, 1995.
  18. Skolnick A.A.: Old Chinese herbal medicine used for fever yields possible new Alzheimer disease therapy. J. Amer. Med. Assoc. 277: 776, 1997. Go to original source...
  19. Tonduli L,S., G. Testylier, C. Masqueliez, G. Lallement, P. Monmaur: Effects of Huperzine used as pre-treatment against soman-induced seizures. Neurotoxicology 22: 29-37, 2001. Go to original source... Go to PubMed...
  20. Ved H.S., M.L. Koenig, J.R. Dave, B.P. Doktor: Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Neuroreport 8: 963-968, 1997. Go to original source... Go to PubMed...
  21. Yuan S.Q. and T.T. Wei: Studies on the alkaloids of Huperzia serrata (Thunb.) Trev. [Article in Chinese]. Yao Xue Xue Bao 23: 516-520, 1988. Go to PubMed...