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DOI: 10.1039/A807387B (Paper) Reference Section for: Analyst, 1998, 123, 2835-2837

Directly coupled CZE-NMR and CEC-NMR spectroscopy for metabolite analysis: paracetamol metabolites in human urine

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Jens Schewitz, Petra Gfrörer, Klaus Pusecker, Li-Hong Tseng, Klaus Albert, Ernst Bayer, Ian D. Wilson, Nigel J. Bailey, Graeme B. Scarfe, Jeremy K. Nicholson and John C. Lindon

Abstract

Direct coupling of NMR spectroscopic detection with both capillary zone electrophoresis (CZE) and capillary electrochromatography (CEC) was applied to the separation of metabolites of the drug paracetamol in an extract of human urine. Continuous-flow CZE-NMR and CEC-NMR allowed the detection of the major metabolites, the glucuronide and sulfate conjugates of the drug and the endogenous material hippurate. Identification of these substances was achieved by examination of individual rows of the NMR chromatogram and this also gave estimates of the detection limits. For CEC-NMR, spectra were also obtained in the stopped-flow mode including a two-dimensional TOCSY NMR experiment which afforded confirmatory evidence for paracetamol glucuronide. Characterisation of drug metabolites using NMR spectroscopy is therefore possible with nanolitre sample volumes.

References

  1. J. C. Lindon, J. K. Nicholson and I. D. Wilson, Adv. Chromatogr., 1995, 36, 315.
  2. J. C. Lindon, J. K. Nicholson, U. G. Sidelmann and I. D. Wilson, Drug Metab. Rev., 1997, 29, 705 CAS.
  3. A. Holtzel, G. Schlotterbeck, K. Albert and E. Bayer, Chromatographia, 1996, 42, 499.
  4. G. Schlotterbeck, L.-H. Tseng, H. Handel, U. Braumann and K. Albert, Anal. Chem., 1997, 69, 1421 CrossRef CAS.
  5. S. Strohschein, M. Pursch, H. Handel and K. Albert, Fresenius' J. Anal. Chem., 1997, 357, 498 CrossRef CAS.
  6. J. C. Lindon, R. D. Farrant, P. N. Sanderson, P. M. Doyle, S. L. Gough, M. Spraul, M. Hofmann and J. K. Nicholson, Magn. Reson. Chem., 1995, 33, 857 CAS.
  7. F. S. Pullen, A. G. Swanson, M. J. Newman and D. S. Richards, Rapid Commun. Mass Spectrom., 1995, 9, 1003 CAS.
  8. J. P. Shockcor, S. E. Unger, I. D. Wilson, P. J. D. Foxall, J. K. Nicholson and J. C. Lindon, Anal. Chem., 1996, 68, 4431 CrossRef.
  9. N. Wu, A. G. Webb, T. L. Peck and J. V. Sweedler, Anal. Chem., 1995, 67, 3101 CrossRef CAS.
  10. B. Behnke, G. Schlotterbeck, U. Tallarek, S. Strohschein, L.-H. Tseng, T. Keller, K. Albert and E. Bayer, Anal. Chem., 1996, 68, 1110 CrossRef CAS.
  11. N. Wu, T. L. Peck, A. G. Webb, R. L. Magin and J. V. Sweedler, Anal. Chem., 1994, 66, 3849 CrossRef CAS.
  12. N. Wu, T. L. Peck, A. G. Webb, R. L. Magin and J. V. Sweedler, J. Am. Chem. Soc., 1994, 116, 7929 CrossRef CAS.
  13. K. Albert and E. Bayer, Anal. Methods Instrum., 1995, 2, 302 Search PubMed.
  14. K. Albert, J. Chromatogr. A, 1995, 703, 123 CrossRef CAS.
  15. J. C. Lindon, J. K. Nicholson and I. D. Wilson, Prog. Nucl. Magn. Reson. Spectrosc., 1996, 29, 1 CrossRef CAS.
  16. K. Pusecker, J. Schewitz, P. Gfrörer, L.-H. Tseng, K. Albert and E. Bayer, Anal. Chem., 1998, 70, 3280 CrossRef CAS.
  17. K. Pusecker, J. Schewitz, P. Gfrörer, L.-H. Tseng, K. Albert, E. Bayer, I. D. Wilson, N. J. Bailey, G. B. Scarfe, J. K. Nicholson and J. C. Lindon, Anal. Commun., 1998, 35, 213 RSC.
  18. J. R. Bales, P. J. Sadler, J. K. Nicholson and J. A. Timbrell, Clin. Chem., 1984, 30, 1631 CAS.
  19. J. R. Bales, J. K. Nicholson and P. J. Sadler, Clin. Chem., 1985, 31, 757 CAS.
  20. M. Spraul, M. Hofmann, J. C. Lindon, R. D. Farrant, M. J. Seddon, J. K. Nicholson and I. D. Wilson, NMR Biomed., 1994, 7, 295 CAS.
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