Skip to main content

Advertisement

SpringerLink
Log in

Hyphenation of reverse-phase HPLC and ICP-MS for metabolite profiling—application to a novel antituberculosis compound as a case study

  • Technical Note
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

In this study, a high-performance liquid chromatography (HPLC) inductively coupled plasma (ICP) mass spectrometry (MS) method was developed intended for use in metabolism studies of bromine-containing drugs, administered to test animals (or test persons). As a case study, the method was applied to a new antituberculosis compound, the bromine-containing diarylquinoline R207910. A method has been proposed to overcome the incompatibilities between the high organic solvent content (45%CH3OH and 45% CH3CN) used in the reverse-phase liquid chromatography (LC) separation on one hand and the limitations of the ICP on the other hand. Therefore, several instrument modifications had to be made. For the introduction of the column effluent, a combination of a perfluoroalkoxy LC nebulizer with a PC3 Peltier-cooled inlet system (operated at 2 °C) was used. Additionally, the standard injector tube (internal diameter 2 mm) was replaced by an injector tube with an internal diameter of 1 mm and to avoid carbon build-up on the interface cones and the torch, the nebulizer gas was admixed with 6% v/v of oxygen. After optimization of the method, HPLC-ICP-MS was applied for metabolite profiling of faeces samples after dosing of 14C-radiolabelled R207910 to dogs and rats. To evaluate the method developed, the HPLC-ICP-MS results were compared with those of HPLC with UV spectrophotometric and 14C radiochemical detection. As the HPLC-ICP-MS method gave rise to a higher selectivity than HPLC with UV detection and to a better detection limit (5 ng R207910) than the method with radiochemical detection (65 ng R207910), it can be concluded that ICP-MS can be used as a good alternative to the more traditional detection methods, even when a mobile phase with high organic solvent content has to be used in the LC separation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. National Centre for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of Tuberculosis Elimination (2005) Questions and answers about TB 2005. http://www.cdc.gov/tb/faqs/qa_introduction.htm

  2. World Health Organization (2004) Further information on spinal, gastrointestinal and hepatic TB. http://whqlibdoc.who.int/publications/2004/9241546344.pdf

  3. Global Alliance for TB Drug Development (2007) TB Alliance. http://www.tballiance.org

  4. Andries K, Verhasselt P, Guillemont J, Göhlmann HWH, Neefs J, Winkler H, Van Gestel J, Timmerman P, Zhu M, Lee E, Williams P, de Chaffoy D, Huitric E, Hoffner S, Cambau E, Truffot-Pernot C, Lounis N, Jarlier V (2005) Science 307:223–227

    Article  CAS  Google Scholar 

  5. Wind M, Lehmann WD (2004) J Anal At Spectrom 19:20–25

    Article  CAS  Google Scholar 

  6. Blades MW, Caughlin BL (1985) Spectrochim Acta Part B 40:579–591

    Article  Google Scholar 

  7. Boorn AW, Browner RF (1982) Anal Chem 54:1402–1410

    Article  CAS  Google Scholar 

  8. Bendahl L, Gammelgaard B (2005) J Anal At Spectrom 20:410–416

    Article  CAS  Google Scholar 

  9. Gammelgaard B, Jensen BP (2007) J Anal At Spectrom 22:235–249

    Article  CAS  Google Scholar 

  10. Wind M, Eisenmenger A, Lehmann WD (2002) J Anal At Spectrom 17:21–26

    Article  CAS  Google Scholar 

  11. Ackley KL, Sutton KL, Caruso JA (2000) J Anal At Spectrom 15:1069–1073

    Article  CAS  Google Scholar 

  12. Stefánka Z, Koellensperger G, Stingeder G, Hann S (2006) J Anal At Spectrom 21:86–89

    Article  Google Scholar 

  13. Kannamkumarath SS, Wuilloud RG, Stalcup A, Caruso JA, Patel H, Sakr A (2004) J Anal At Spectrom 19:107–113

    Article  CAS  Google Scholar 

  14. Hill SJ, Hartley J, Ebdon L (1992) J Anal At Spectrom 7:23–28

    Article  CAS  Google Scholar 

  15. Makarov A, Szpunar J (1999) J Anal At Spectrom 14:1323–1327

    Article  CAS  Google Scholar 

  16. Jensen BP, Gammelgaard B, Hansen SH, Andersen JV (2003) J Anal At Spectrom 18:891–896

    Article  CAS  Google Scholar 

  17. Kishi Y, Kawabata K, Shi H, Thomas R (2004) Spectroscopy 19:14–22

    CAS  Google Scholar 

  18. Smith CJ, Wilson ID, Abou-Shakra F, Payne R, Grisedale H, Long A, Roberts D, Malone M (2002) Chromatographia 55:S151–S155

    Article  CAS  Google Scholar 

  19. Jensen BP, Gammelgaard B, Hansen SH, Andersen JV (2005) J Anal At Spectrom 20:204–209

    Article  CAS  Google Scholar 

  20. Abou-Shakra FR, Sage AB, Castro-Perez J, Nicholson JK, Lindon JC, Scarfe GB, Wilson ID (2002) Chromatographia 55:S9–S13

    Article  CAS  Google Scholar 

  21. Jensen BP, Smith CJ, Bailey CJ, Rodgers C, Wilson ID, Nicholson JK (2005) Rapid Commun Mass Spectrom 19:519–524

    Article  CAS  Google Scholar 

  22. Barrett P, Pruszkowska E (1984) Anal Chem 56:1927–1930

    Article  CAS  Google Scholar 

  23. Jarvis KE, Gray AL, Houk RS (2003) Handbook of inductively coupled plasma mass spectrometry. Viridian, Woking

    Google Scholar 

  24. Rosman KJR, Taylor PDP (1999) J Anal At Spectrom 14:5N

    Google Scholar 

  25. Kawai T, Zhang ZW, Moon CS, Shimbo S, Watanabe T, Matsuda-Inoguchi N, Higashikawa K, Ikeda M (2002) Toxicol Lett 134:285–293

    Article  CAS  Google Scholar 

  26. Rottmann L, Heumann KG (1994) Fresenius J Anal Chem 350:221–227

    Article  CAS  Google Scholar 

Download references

Acknowledgements

L.I.L.B. is a Senior Research Assistant of the Fund for Scientific Research—Flanders (FWO-Vlaanderen). F.V. acknowledges the FWO-Vlaanderen for financial support (research project G.0669.06).

Author information

Authors and Affiliations

  1. Department of Analytical Chemistry, Ghent University, Proeftuinstraat 86, 9000, Ghent, Belgium

    Lieve I. L. Balcaen, Björn De Samber, Kenny De Wolf & Frank Vanhaecke

  2. Global Preclinical Development, Johnson & Johnson Pharmaceutical R&D, Turnhoutseweg 30, 2340, Beerse, Belgium

    Filip Cuyckens

Authors
  1. Lieve I. L. Balcaen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Björn De Samber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenny De Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Filip Cuyckens
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Frank Vanhaecke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frank Vanhaecke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balcaen, L.I.L., De Samber, B., De Wolf, K. et al. Hyphenation of reverse-phase HPLC and ICP-MS for metabolite profiling—application to a novel antituberculosis compound as a case study. Anal Bioanal Chem 389, 777–786 (2007). https://doi.org/10.1007/s00216-007-1303-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-007-1303-2

Keywords

Search

Navigation