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Analysis of dihydroartemisinin in plasma by liquid chromatography—Mass spectrometry

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Summary

Artemisinin (ART), or qinghaosu, a sesquiterpene lactone containing an endoperoxide bridge, is an efficient drug against chloroquine-resistant strains ofPlasmodium falciparum in the treatment of cerebral malaria. ART and its derivatives are rapidly metabolized into dihydroartemisinin (DHA), which is responsible for the antimalarial activity. After a simple liquid-liquid extraction (LLE), determination of DHA in plasma was conducted by liquid chromatography-mass spectrometry (LC-MS) with an electrospray ionization (ESI) interface. Addition of dodecylamine to the mobile phase and analysis in selected-ion monitoring (SIM) mode resulted in enhanced sensitivity and selectivity. Use of a primary amine, e.g. propylamine, pentylamine, hexylamine or dodecylamine, in the mobile phase can inhibit the formation of multimer clusters and ion adducts by forming one dominating species (analyte-primary amine adduct). Dodecylamine (DDA) was selected after several assays as a competitive agent for adduct formation. The procedure was validated and precision and accuracy were found to be good for the matrix studied. The method was applied to samples provided by patients receiving artesunate (ARS) for antimalarial treatment.

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References

  1. Klayman, D.L.Science 1985,228, 1049–1055.

    Article  CAS  Google Scholar 

  2. Batty, K.T.; Thu, L.T.; Davis, T.M.; Ilett, K.F.; Mai, T.X.; Hung, N.C.; Tien, N.P.; Powell, S.M.; Thien, H.V.; Binh, T.Q.; Kim, N.V.Br. J. Clin. Pharmacol 1998,45, 123–129.

    Article  CAS  Google Scholar 

  3. China Cooperative Research Group on Qinghaosu and its derivatives as antimalarils.J. Trad. Chin. Med. 1982,2, 25–30.

    Google Scholar 

  4. China Cooperative Research Group on Qinghaosu and its derivatives as antimalarials.J. Trad. Chin. Med. 1982,2, 17–24.

    Google Scholar 

  5. de Vries, P.J.; Dien, T.K.Drugs 1996,52, 818–836.

    Google Scholar 

  6. Hassan, A.M.; Ashton, M.; Kihamia, C.M.; Mtey, G.J.; Bjorkman, A.Trans. Royal Soc. Trop. Med. Hyg. 1996,90, 61–65.

    Article  Google Scholar 

  7. White, N.J.Trans. Royal Soc. Trop. Med. Hyg. 1994,88,Suppl 1, S41-S43.

    Article  Google Scholar 

  8. Ravindranathan, T.; Kumar, M.A.; Menon, R.B.; Hiremath, S.V.Tetrahedron Lett. 1990,31, 755–758.

    Article  CAS  Google Scholar 

  9. Guo-Qiao, L.; Xing-Bo, G.; Lin-Chun, F.; Hua-Xiang, J.; Xin-Hua, W.Trans. Royal Soc. Trop. Med. Hyg. 1994,88,Suppl 1, S5-S6.

    Google Scholar 

  10. Kohler, M.; Haerdi, W.; Christen, P.; Veuthey, J.-L.Phytochem. Anal. 1997,8, 223–227.

    Article  CAS  Google Scholar 

  11. Benakis, A.; Schopfer, C.; Paris, M.; Plessas, C.T.; Karayannakos, P.E.; Dondas, I.; Kotsarelis, D.; Plessas, S.T.; Skalkeas, G.Eur. J. Drug Metab. Pharm. 1991,16, 325–328.

    Article  CAS  Google Scholar 

  12. Benakis, A.; Paris, M.; Loutan, L.; Plessas, C.T.; Plessas, S.T.Am. J. Trop. Med. Hyg. 1999,56, 17–23.

    Google Scholar 

  13. Ferreira, J.F.S.; Charles, D.J.; Wood, K.; Janick, J.; Simon, J.E.Phytochem. Anal. 1994,5, 116–120.

    CAS  Google Scholar 

  14. Karbwang, J.; Na-Bangchang, K.; Molunto, P.; Banmairuroi, V.; Congpuong, K.J. Chromatogr. B 1997,690, 259–265.

    CAS  Google Scholar 

  15. Melendez, V.; Peggins, J.O.; Brewer, T.G.; Theoharides, A.D.J. Pharm. Sci. 1991,80, 132–138.

    Article  CAS  Google Scholar 

  16. Navaratnam, V.; Mansor, S.M.; Chin, L.K.; Mordi, M.N.; Asokan, M.; Nair, N.K.J. Chromatogr. B 1995,669, 289–294.

    CAS  Google Scholar 

  17. Navaratnam, V.; Mordi, M.N.; Mansor, S.M.J. Chromatogr. B 1997,692, 157–162.

    CAS  Google Scholar 

  18. Sandrenan, N.; Sioufi, A.; Godbillon, J.; Netter, C.; Donker, M.; van Valkenburg, C.J. Chromatogr. B 1997,691, 145–153.

    CAS  Google Scholar 

  19. Teja-Isavadharm, P.; Nosten, F.; Kyle, D.E.; Luxemburger, C.; Ter Kuile, F.; Peggins, J.O.; Brewer, T.G.; White, N.J.Br. J. Clin. Pharmacol. 1996,42, 599–604.

    CAS  Google Scholar 

  20. van Agtmael, M.A.; Butter, J.J.; Portier, E.J.; van Boxtel, C.J.Ther. Drug Monitoring 1998,20, 109–116.

    Article  Google Scholar 

  21. Zhou, Z.M.; Anders, J.C.; Chung, H.; Theoharides, A.D.J. Chromatogr. 1987,414, 77–90.

    CAS  Google Scholar 

  22. Theoharides, A.D.; Smyth, M.; Ashmore, R.; Halverson, J.; Zhou, Z.; Ridder, W.; Lin, A.Anal. Chem. 1988,60, 115–120.

    Article  CAS  Google Scholar 

  23. Mohamed, S.S.; Khalid, S.A.; Ward, S.A.; Wan, T.S.M.; Tang, H.P.O.; Zheng, M.; Haynes, R.K.; Edwards, G.J. Chromatogr. B 1999,731, 251–260.

    CAS  Google Scholar 

  24. Mount, D.L.; Todd, G.D.; Navaratnam, V.J. Chromatogr. B 1995,666, 183–187.

    CAS  Google Scholar 

  25. Song, Z.Y.; Zhao, K.C.; Liang, X.T.; Liu, C.X.; Yi, M.G.Acta Pharm Sinica 1985,20, 610–614.

    CAS  Google Scholar 

  26. Hoja, H.; Marquet, P.; Verneuil, B.; Lotfi, H.; Penicaut, B.; Lachatre, G.J. Anal. Toxicol. 1997,21, 116–126.

    CAS  Google Scholar 

  27. Lee, M.S.; Kerns, E.H.; Hail, M.E.; Liu, J.; Volk, K.J.LC-GC 1997,15, 542–558.

    CAS  Google Scholar 

  28. Maurer, H.H.J. Chromatogr. B 1998,713, 3–25.

    CAS  Google Scholar 

  29. Nishikawa, M.; Tsuchihashi, H.J. Toxicol. 1998,17, 13–26.

    CAS  Google Scholar 

  30. Zhou, S.; Hamburger, M.J. Chromatogr. A 1996,755, 189–204.

    Article  CAS  Google Scholar 

  31. Sahai, P.; Vishwakarma, R.A.; Bharel, S.; Gulati, A.; Abdin, M.Z.; Srivastava, P.S.; Jain, S.K.Anal. Chem. 1998,70, 3084–3087.

    Article  CAS  Google Scholar 

  32. Maggs, J.L.; Madden, S.; Bishop, L.P.; O'Neill, P.M.; Park, B.K.Drug Metab. Disp. 1997,25, 1200–1204.

    CAS  Google Scholar 

  33. Chi, H.T.; Ramu, K.; Baker, J.K.; Hufford, C.D.; Lee, I.-S.; Yan-Lin, Z.; McChesney, J.D.Biol. Mass Spectrom. 1991,20, 609–628.

    Article  CAS  Google Scholar 

  34. Chapuzet, E.; Mercier, N.; Bevoas-Martin, S.; Boulanger, B.; Chevalier, P.; Chiap, P.; Grandjean, D.; Hubert, P.; Lagorce, P.; Lallier, M.; Laparra, M.C.; Laurentie, M.; Nivet, J.C.S. T. P. Pharma Pratiques 1997,7, 169–194.

    CAS  Google Scholar 

  35. W.M.A. Niessen Liquid Chromatography-Mass Spectrometry, Marcel Dekker, New York,1999.

    Google Scholar 

  36. Stefansson, M.; Sjöberg, P.J.R.; Markides, K.E.Anal. Chem. 1996,68, 1792–1797.

    Article  CAS  Google Scholar 

  37. Muhia, D.K.; Mberu, E.K.; Watkins, W.M.J. Chromatogr. B 1994,660, 196–199.

    CAS  Google Scholar 

  38. Edlund, P.O.; Westerlund, D.; Carlqvist, J.; Wu, B.L.; Jin, Y.H.Acta Pharm. Suecica 1984,21, 223–234.

    CAS  Google Scholar 

  39. Bangchang, K.N.; Karbwang, J.; Thomas, C.G.; Thanavibul, A.; Sukontason, K.; Ward, S.A.; Edwards G.Br. J. Clin. Pharmacol. 1994,37, 249–253.

    CAS  Google Scholar 

  40. Batty, K.T.; Davis, T.M.; Thu, L.T.; Binh, T.Q.; Anh, T.K.; Ilett, K.F.J. Chromatogr. B 1996,677, 345–350.

    Google Scholar 

  41. Hubert, P.; Chiap, P.; Crommen, J.; Boulanger, B.; Chapuzet, E.; Mercier, N.; Bervoas-Martin, S.; Chevalier, P.; Grandjean, D.; Lagorce, P.; Lallier, M.; Laparra, M.C.; Laurentie, M.; Nivet, J.C.Analytica Chimica Acta 1999,391, 135–148.

    Article  CAS  Google Scholar 

  42. Shah, V.P.; Midha, K.K.; Dighe, S.; McGilveray, I.J.; Skelly, J.P.; Yacobi, A.; Layloff, T.; Viswanathan, C.T.; Cook, C.E.; McDowall, R.D.; Pittman, K.A.; Spector, S.Int. J. Pharmaceutics 1992,82, 1–7.

    Article  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Analytical Chemistry, University of Geneva, Bd. d'Yvoy 20, 1211, Geneva 4, Switzerland

    D. Ortelli, S. Rudaz, E. Cognard & J. -L. Veuthey

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  1. D. Ortelli
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  2. S. Rudaz
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  3. E. Cognard
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  4. J. -L. Veuthey
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Ortelli, D., Rudaz, S., Cognard, E. et al. Analysis of dihydroartemisinin in plasma by liquid chromatography—Mass spectrometry. Chromatographia 52, 445–450 (2000). https://doi.org/10.1007/BF02535717

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  • DOI: https://doi.org/10.1007/BF02535717

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