Analytical and Bioanalytical Chemistry

, Volume 381, Issue 2, pp 405–412 | Cite as

Novel separation method for highly sensitive speciation of cancerostatic platinum compounds by HPLC–ICP–MS

  • S. HannEmail author
  • Zs. Stefánka
  • K. Lenz
  • G. Stingeder
Special Issue Paper


A high-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC–ICP–MS) method is presented for analysis of cisplatin, monoaquacisplatin, diaquacisplatin, carboplatin, and oxaliplatin in biological and environmental samples. Chromatographic separation was achieved on pentafluorophenylpropyl-functionalized silica gel. For cisplatin, carboplatin, and oxaliplatin limits of detection of 0.09, 0.10, and 0.15 μg L−1, respectively, were calculated at m/z 194, using aqueous standard solutions. (3 μL injection volume). The method was utilized for model experiments studying the stability of carboplatin and oxaliplatin at different chloride concentrations simulating wastewater and surface water conditions. It was found that a high fraction of carboplatin is stable in ultrapure water and in solutions containing 1.5 mol L−1 Cl, whereas oxaliplatin degradation was increased by increasing the chloride concentration. In order to support the assessment of oxaliplatin eco-toxicology, the method was tested for speciation of patient urine. The urine sample contained more than 17 different reaction products, which demonstrates the extensive biotransformation of the compound. In a second step of the study the method was successfully evaluated for monitoring cancerostatic platinum compounds in hospital waste water.


Cisplatin Carboplatin Oxaliplatin Wastewater Urine Stability study 



Financial support was granted through the Austrian Science Fund (FWF-Project P16089-N03: “Speciation of cancerostatic Pt compounds in the environment”). Professor Robert Mader (Vienna University Hospital) is gratefully acknowledged for sampling of patient urine.


  1. 1.
    Roberts JJ, Thomson AJ (1979) Prog Nucleic Acid Res Mol Biol 22:71PubMedGoogle Scholar
  2. 2.
    Pineto HM, Schornagel JH (eds) (1996) Platinum and other metal coordination compounds in cancer chemotherapy 2. Plenum, New YorkGoogle Scholar
  3. 3.
    Desoize B and Madoulet C (2002) Crit Rev Oncol Hematol 42:317–325CrossRefPubMedGoogle Scholar
  4. 4.
    Allwood M, Stanley A, Wright P (eds) (1997) The cytotoxics handbook. Radcliffe Medical Press, AbingdonGoogle Scholar
  5. 5.
    Dorr RT, Von Hoff DD (1994) Cancer chemotherapy book. McGraw–Hill, ColumbusGoogle Scholar
  6. 6.
    Graham MA, Gamelin E, Misset JL, Brienza S, Allain P, Boisdron-Celle, Krikorian A, Greenslade D, Bayssas M (1998) Proc Am Assoc Cancer Res 39:159Google Scholar
  7. 7.
    Mahnik S, Mader R, Fürhacker M (2002) ÖWAV Workshop: Arzneimittel in der aquatischen Umwelt, 26.9.2002, Universität für Bodenkultur Wien; Zytostatika im Abwasser. Wiener Mitteilungen 178:91–111Google Scholar
  8. 8.
    International Agency for Research on Cancer (IARC), (1987) Monographs on the Evaluation of Cancerogenic Risks to Humans, suppl 7, LyonGoogle Scholar
  9. 9.
    Gebel T (2000) AAAa. In: Zereini F, Alt F (eds) Anthropogenic platinum group element emissions. Springer Verlag, Berlin Heidelberg New York, pp 245–255Google Scholar
  10. 10.
    Heudi O, Cailleux A, Allain P (1998) J Inorg Biochem 71:61–69CrossRefGoogle Scholar
  11. 11.
    Pujol M, Girona V, Prat J, Munoz M, De Bolos J (1997) Int J Pharm 146:263–269CrossRefGoogle Scholar
  12. 12.
    Schnurr B, Gust R (2002) Microchim Acta 140:69–76CrossRefGoogle Scholar
  13. 13.
    Jerremalm E, Videhult P, Alvelius G, Griffiths WJ, Bergman T, Eksborg S, Ehrsson H (2002) J Pharm Sci 91:2116–2121CrossRefPubMedGoogle Scholar
  14. 14.
    El-Khateeb M, Appleton TG, Gahan LR, Charles BG, Berners-Price SJ, Bolton A (1999) J Inorg Biochem 77:13–21CrossRefPubMedGoogle Scholar
  15. 15.
    Zhao Z, Tepperman K, Dorsey JG, Elder RC (1993) J Chromatogr 615:83–89CrossRefPubMedGoogle Scholar
  16. 16.
    Cairns WRL, Ebdon L, Hill SJ (1996) Fresenius J Anal Chem 355:202CrossRefGoogle Scholar
  17. 17.
    Hann S, Zenker A, Galanski M, Bereuter TL, Stingeder G, Keppler BK (2001) Fresenius J Anal Chem 370:581–586CrossRefPubMedGoogle Scholar
  18. 18.
    Vacchina V, Torti L, Allievi C, Lobinski R (2003) J Anal At Spectrom 18:884–890CrossRefGoogle Scholar
  19. 19.
    Luo FR, Yen T-Y, Wyrick SD, Chaney SG (1999) J Chromatogr B 724:345–356CrossRefGoogle Scholar
  20. 20.
    Burns RB, Burton RW, Albon SP, Embree L (1996) J Pharm Biomed Anal 14:367–372CrossRefPubMedGoogle Scholar
  21. 21.
    Küng A, Strickmann DB, Galanski M, Keppler BK (2001) J Inorg Biochem 86:691–698CrossRefPubMedGoogle Scholar
  22. 22.
    Lederer M, Leipzig-Pagani E (1998) Int J Pharm 167:223–228CrossRefGoogle Scholar
  23. 23.
    Ehrsson H, Wallin I (2003) J Chromatogr B 795:291–294CrossRefGoogle Scholar
  24. 24.
    Zenker A, Galanski M, Bereuter TL, Keppler BK, Lindner W (2000) J Chromatogr B 745:211–219CrossRefGoogle Scholar
  25. 25.
    De Waal WAJ, Maessen FJMJ, Kraak JC (1987) J Chromatogr 407:253–272CrossRefPubMedGoogle Scholar
  26. 26.
    Lenz K, Hann S, Koellensperger G, Stefanka Zs, Stingeder G, Weissenbacher N, Mahnik SN, Fuerhacker M, J Environ Monit (submitted)Google Scholar
  27. 27.
    Falter R, Wilken RD (1999) Sci Total Environ 225:167–176CrossRefPubMedGoogle Scholar
  28. 28.
    Hann S, Koellensperger G, Stefánka Zs, Stingeder G, Fürhacker M, Buchberger W, Mader RM (2003) J Anal At Spectrom 18:1391–1395CrossRefGoogle Scholar
  29. 29.
    Stefánka Zs, Hann S, Koellensperger G, Stingeder G (2004) J Anal At Spectrom. DOI:10.1039/B402028FGoogle Scholar
  30. 30.
    Kiffmeyer T, Götze HJ, Jursch M, Lüders U (1998) Fresenius J Anal Chem 361:185–191CrossRefGoogle Scholar
  31. 31.
    Quantifying Uncertainty in Analytical Measurement (2000) EURACHEM, LondonGoogle Scholar
  32. 32.
    Davies MS, Berners-Price SJ, Hambley TW (2000) Inorg Chem 39:5603–5613CrossRefPubMedGoogle Scholar
  33. 33.
    Hindmarsch K, House DA, Turnbull MM (1997) Inorg Chim Acta 39:11–18CrossRefGoogle Scholar
  34. 34.
    Gust R, Schnurr B (1999) Chem Monthly 130:637–644CrossRefGoogle Scholar
  35. 35.
    Tang X, Hayes II JW, Schroder L, Cacini W, Dorsey J, Elder RC, Tepperman K (1997) Met Based Drugs 4:97–109Google Scholar
  36. 36.
    Jerremalm E, Hedeland M, Wallin I, Bondesson U, Ehrsson H (2004) Pharm Res 21:891–894CrossRefPubMedGoogle Scholar
  37. 37.
    Graham MA, Lockwood GF, Greenslade D, Brienza S, Bayssas M, Gamelin E (2000) Clin Cancer Res 6:1205–1218PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of Chemistry, Division of Analytical ChemistryBOKU, University of Natural Resources and Applied Life SciencesViennaAustria

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