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Analytical and Bioanalytical Chemistry

, Volume 408, Issue 24, pp 6789–6797 | Cite as

SFC-MS/MS as an orthogonal technique for improved screening of polar analytes in anti-doping control

  • Maria Kristina Parr
  • Bernhard Wuest
  • Edgar Naegele
  • Jan F. Joseph
  • Maxi Wenzel
  • Alexander H. Schmidt
  • Mijo Stanic
  • Xavier de la Torre
  • Francesco Botrè
Research Paper

Abstract

HPLC is considered the method of choice for the separation of various classes of drugs. However, some analytes are still challenging as HPLC shows limited resolution capabilities for highly polar analytes as they interact insufficiently on conventional reversed-phase (RP) columns. Especially in combination with mass spectrometric detection, limitations apply for alterations of stationary phases. Some highly polar sympathomimetic drugs and their metabolites showed almost no retention on different RP columns. Their retention remains poor even on phenylhexyl phases that show different selectivity due to π–π interactions. Supercritical fluid chromatography (SFC) as an orthogonal separation technique to HPLC may help to overcome these issues. Selected polar drugs and metabolites were analyzed utilizing SFC separation. All compounds showed sharp peaks and good retention even for the very polar analytes, such as sulfoconjugates. Retention times and elution orders in SFC are different to both RP and HILIC separations as a result of the orthogonality. Short cycle times could be realized. As temperature and pressure strongly influence the polarity of supercritical fluids, precise regulation of temperature and backpressure is required for the stability of the retention times. As CO2 is the main constituent of the mobile phase in SFC, solvent consumption and solvent waste are considerably reduced.

Graphical Abstract

SFC-MS/MS vs. LC-MS/MS

Keywords

Sympathomimetic drugs Beta-blockers Polar stimulants Doping control Sulfoconjugates Dilute-and-inject 

Notes

Acknowledgments

The World Anti-Doping Agency is acknowledged for their financial support (research grant 14A03KP). The authors thank Mr. Felix Bredendiek for technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

216_2016_9805_MOESM1_ESM.pdf (36 kb)
ESM 1 (PDF 36.1 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Maria Kristina Parr
    • 1
  • Bernhard Wuest
    • 2
  • Edgar Naegele
    • 2
  • Jan F. Joseph
    • 1
  • Maxi Wenzel
    • 1
  • Alexander H. Schmidt
    • 1
    • 3
  • Mijo Stanic
    • 3
  • Xavier de la Torre
    • 4
  • Francesco Botrè
    • 4
    • 5
  1. 1.Institute of PharmacyFreie Universität BerlinBerlinGermany
  2. 2.Agilent TechnologiesSanta ClaraUSA
  3. 3.Chromicent GmbHBerlinGermany
  4. 4.Laboratorio Antidoping FMSIRomeItaly
  5. 5.Department of Experimental Medicine‘Sapienza’ University of RomeRomeItaly

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