Skip to main content
Log in

Hydroxymethylfurfural: an enemy or a friendly xenobiotic? A bioanalytical approach

  • Original Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Hydroxymethylfurfural (HMF), a well-known heterocyclic Maillard reaction product, has often been studied for its potential toxic, mutagenic, and carcinogenic effects. Recent clinical studies, however, have strongly suggested that HMF might have exciting antitumor potential. We report on the development and validation of a bioanalytical assay for HMF that could be suitable as a basis for pharmacokinetic models in cancer patients. Two strategies were tested, i.e., direct and indirect methodologies. A direct isocratic LC determination at 283 nm was designed. Two indirect attempts involved derivatization coupled to HPLC-UV. It was possible to resolve the stereoisomers of the HMF derivative, and factors influencing their equilibrium ratio are discussed. HMF was extracted from the biomatrix by solid-phase extraction using different cartridges. A comparative study was made of the implemented methods as well as the extraction protocols. Both indirect assays proved to be more sensitive and were used to assess HMF quantitatively in human plasma. However, the newly introduced derivatization conditions led to the highest sensitivity with a LOD (S/N ratio = 3) of at least 2 pmol analyte on column. The assay selectivity was satisfactory in pre- and post-dose real samples. The mean recoveries of the assays were 79% and 89%, with acceptable accuracies and reproducibilities.

Schematic representation of hydroxymethylfurfural (HMF) in human plasma

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Nassberger L (1990) Hum Exp Toxicol 9:211–214

    Article  CAS  Google Scholar 

  2. Ulbricht RJ, Northup SJ, Thomas JA (1984) Fundam Appl Toxicol 4:843–853

    Article  CAS  Google Scholar 

  3. Rasmussen A, Hessov I, Bojsen-Moller M (1982) Acta Pharmacol Toxicol 50:81–84

    Article  CAS  Google Scholar 

  4. Shinohara K, Kim E-H, Omura H (1986) Dev Food Sci 13:353–362

    CAS  Google Scholar 

  5. Kim SB, Hayase F, Kato H (1987) Mutat Res 177:9–15

    CAS  Google Scholar 

  6. Surh YJ, Tannenbaum SR (1994) Chem Res Toxicol 7:313–318

    Article  CAS  Google Scholar 

  7. Janzowski C, Glaab V, Samimi E, Schlatter J, Eisenbrand G (2000) Food Chem Toxicol 38:801–809

    Article  CAS  Google Scholar 

  8. Archer MC, Bruce WR, Chan CC, Corpet DE, Medline A, Roncucci L, Stamp D, Zhang XM (1992) Environ Health Persp 98:195–197

    Article  CAS  Google Scholar 

  9. Zhang XM, Chan CC, Stamp D, Minkin S, Archer MC, Bruce WR (1993) Carcinogenesis 14:773–775

    Article  CAS  Google Scholar 

  10. Miyakawa Y, Nishi Y, Kato K, Sato K, Takahashi M, Hayashi Y (1991) Carcinogenesis 12:1169–1173

    Article  CAS  Google Scholar 

  11. Uckun FM, Shyi-Tai Jan M (2003) US Patent 6,258,841 B1

  12. Ying D, Kevin P, Weihan Z, Xiaoqiang Y, Jianrong H (2005) US Patent 2005 124684 A1

  13. Herwig R (2006) Pilotstudie KARAL- Monochemotherapien. Austrian Patent 393221 B

  14. Rufian-Henares JA, Delgado-Andrade C, Morales FJ (2006) J AOAC Int 89:161–165

    CAS  Google Scholar 

  15. Gökmen V, Acar J (1999) J Chromatogr A 847:69–74

    Article  Google Scholar 

  16. Menez JF, Berthou F, Meskar A, Picart D, Le Bras R, Bardou LG (1984) J Chromatogr A 297:339–350

    Article  CAS  Google Scholar 

  17. Sampietro T, Lenzi S, Giampietro O, Cecchetti P, Masoni A, Navalesi R (1987) Clin Physiol Biochem 5:49–56

    CAS  Google Scholar 

  18. Lo Coco F, Valentini C, Novelli V, Ceccon L (1996) J Chromatogr A 749:95–102

    Article  Google Scholar 

  19. Shah VP, Midha KK, Findlay JW, Hill HM, Hulse JD, McGilveray IJ, McKay G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Pharm Res 17:1551–1557

    Article  CAS  Google Scholar 

  20. Wieling J, Hendriks G, Tamminga WJ, Hempenius J, Mensink CK, Oosterhuis B, Jonkman JHG (1996) J Chromatogr A 730:381–394

    Article  CAS  Google Scholar 

  21. Dadgar D, Burnett PE, Choc MG, Gallicano K, Hooper JW (1995) J Pharm Biomed Anal 13:89–97

    Article  CAS  Google Scholar 

  22. Bressole F, Bromet-Petit M, Audran M (1996) J Chromatogr B 686:3–10

    Article  Google Scholar 

  23. Jencks WP (1959) J Am Chem Soc 81:475–481

    Article  CAS  Google Scholar 

  24. Ragno M (1945) Gazz Chim Ital 75:175–185

    CAS  Google Scholar 

  25. Legradi L (1971) Mikrochim Acta 2:380–383

    Google Scholar 

  26. Uchiyama S, Ando M, Aoyagi S (2003) J Chromatogr A 996:95–102

    Article  CAS  Google Scholar 

  27. Tayyari SM, Speakman JL, Arnold MB, Cai W, Behforouz M (1998) J Chem Soc Perkin Trans 2:2195–2200

    Google Scholar 

  28. Uchiyama S, Matsushima E, Aoyagi S, Ando M (2004) Anal Chim Acta 523:157–163

    Article  CAS  Google Scholar 

  29. Karabatsos GJ, Shapiro BL, Vane FM, Fleming JS, Ratka JS (1963) J Am Chem Soc 85:2784–2788

    Article  CAS  Google Scholar 

  30. Shvo Y, Nahlieli A (1970) Tetrahedron Lett 49:4273–4274

    Article  Google Scholar 

  31. Pichon R, Le Saint J, Courtot P (1981) Tetrahedron 37:1517–1524

    Article  CAS  Google Scholar 

  32. Clarke LF, O’Sullivan F, Hegarty AF (1991) J Chem Soc Perkin Trans 2 1649–1652

    Google Scholar 

  33. Dadgar D, Burnett PE (1995) J Pharm Biomed Anal 14:23–31

    Article  CAS  Google Scholar 

  34. Braddock LI, Garlow KY, Grim LI, Kirkpatrick AF, Pease SW, Pollard AJ, Price EF, Reissmann TL, Rose HA, Willard ML (1953) Anal Chem 25:301–306

    Article  CAS  Google Scholar 

  35. Ramirez F, Kirby AF (1954) J Am Chem Soc 76:1037–1044

    Article  CAS  Google Scholar 

  36. Karnes HT, Shiu G, Shah VP (1991) Pharm Res 8:421–426

    Article  CAS  Google Scholar 

  37. Shah VP, Midha KK, Dighe S, McGilveray IJ, Skelly JP, Yacobi A, Layloff T, Viswanathan CT, Cook CE, McDowall RD, Pittman KA (1992) J Pharm Sci 81:309–312

    Article  Google Scholar 

  38. Chapuzet E, Mercier N, Bervoas-Martin S, Boulanger B, Chevalier P, Chiap P, Grandjean D, Hubert P, Lagorce P, Lallier M, Laparra MC, Laurentie M, Nivet JC (1998) STP Pharm Prat 8:81–107

    CAS  Google Scholar 

  39. IUPAC (1997) Compendium of analytical nomenclature. Blackwell Science, Oxford

    Google Scholar 

  40. USEPA (2004) Revised assessement of detection and quatitation approaches. US Environmental Protection Agency Document EPA-821-B-04-005, Office of Science and Technology, Washington DC

  41. Jellum E, Børresen HC, Eldjarn L (1973) Clin Chim Acta 47:191–201

    Article  CAS  Google Scholar 

  42. Germond JE, Philippossian G, Richli U, Bracco I, Arnaud MJ (1987) J Toxicol Env Health 22:79–89

    Article  CAS  Google Scholar 

  43. Parkash MK, Caldwell J (1994) Food Chem Toxicol 32:887–895

    Article  CAS  Google Scholar 

  44. Grubbs FE (1969) Technometrics 11:1–21

    Article  Google Scholar 

  45. Chow S-C, Liu J-P (1995) Statistical design and analysis in pharmaceutical sciences: validation and monographs, vol 143. Marcel Dekker, New York

    Google Scholar 

  46. Hartmann C, Smeyers-Verbeke J, Massart DL, Mcdowall RD (1998) J Pharm Biomed Anal 17:193–218

    Article  CAS  Google Scholar 

  47. Hartmann C, Penninckx W, Vander Heyden Y, Vankeerberghen P, Massart DL, McDowall RD (1995) Experience with chromatographic methods-Europe. Blume HH, Midha KK (eds) Bio-international 2. Medpharm Scientific, Stuttgart

    Google Scholar 

  48. International Organization for Standardization (ISO) 5725-1 (1994) Accuracy (trueness and precision) of the results and methods of measurement, Part I: general principles and definitions. ISO, Geneva, Switzerland

  49. Hubert P, Nguyen-Huu JJ, Boulanger B, Chapuzet E, Chiap P, Laurentie M, Mercier N, Muzard G, Nivet C, Valat L (2003) STP Pharm Prat 13:101–138

    Google Scholar 

  50. Satterthwaite FE (1946) Biometrics Bull 2:110–114

    Article  CAS  Google Scholar 

  51. Food and Drug Administration (2001) Guidance for industry: bioanalytical method validation. US Food and Drug Administration, Washington DC, http://www.fda.gov/cder/guidance

  52. International Conference on Harmonization (2005) Validation of analytical procedures: text and methodology Q2(R1), ICH harmonized tripartite guideline, http://www.ich.org/LOB/media/MEDIA417

  53. Vander Heyden Y, Nijhuis A, Smeyers-Verbeke J, Vandegnste BGM, Massart DL (2001) J Pharm Biomed Anal 24:723–753

    Article  Google Scholar 

Download references

Acknowledgments

We are very grateful to C.Y.L. Pharmazeutika Gmbh especially Ch. Buecherl and P. Moser for the partial financial support of this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Wintersteiger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michail, K., Matzi, V., Maier, A. et al. Hydroxymethylfurfural: an enemy or a friendly xenobiotic? A bioanalytical approach. Anal Bioanal Chem 387, 2801–2814 (2007). https://doi.org/10.1007/s00216-007-1121-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-007-1121-6

Keywords

Navigation