Skip to main content
SpringerLink
Log in

Development of the first metabolite-based LC-MSn urine drug screening procedure-exemplified for antidepressants

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

Abstract

In contrast to GC-MS libraries, currently available LC-MS libraries for toxicological detection contain besides parent drugs only some main metabolites limiting their applicability for urine screening. Therefore, a metabolite-based LC-MSn screening procedure was developed and exemplified for antidepressants. The library was built up with MS2 and MS3 wideband spectra using an LXQ linear ion trap with electrospray ionization in the positive mode and full-scan information-dependent acquisition. Pure substance spectra were recorded in methanolic solution and metabolite spectra in urine from rats after administration of the corresponding drugs. After identification, the metabolite spectra were added to the library. Various drugs and metabolites could be sufficiently separated. Recovery, process efficiency, matrix effects, and limits of detection for selected drugs were determined using protein precipitation. Automatic data evaluation was performed using ToxID and SmileMS software. The library consists of over 700 parent compounds including 45 antidepressants, over 1,600 metabolites, and artifacts. Protein precipitation led to sufficient results for sample preparation. ToxID and SmileMS were both suitable for target screening with some pros and cons. In our study, only SmileMS was suitable for untargeted screening being not limited to precursor selection. The LC-MSn method was suitable for urine screening as exemplified for antidepressants. It also allowed detecting unknown compounds based on known fragment structures. As ion suppression can never be excluded, it is advantageous to have several targets per drug. Furthermore, the detection of metabolites confirms the body passage. The presented LC-MSn method complements established GC-MS or LC-MS procedures in the authors’ lab.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Maurer HH, Pfleger K, Weber AA (2007) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim

    Google Scholar 

  2. Meyer MR, Peters FT, Maurer HH (2010) Clin Chem 56:575–584

    Article  CAS  Google Scholar 

  3. Rittner M, Pragst F, Bork WR, Neumann J (2001) J Anal Toxicol 25:115–124

    CAS  Google Scholar 

  4. Weinmann W, Stoertzel M, Vogt S, Wendt J (2001) J Chromatogr A 926:199–209

    Article  CAS  Google Scholar 

  5. Venisse N, Marquet P, Duchoslav E, Dupuy JL, Lachatre G (2003) J Anal Toxicol 27:7–14

    CAS  Google Scholar 

  6. Kratzsch C, Weber AA, Peters FT, Kraemer T, Maurer HH (2003) J Mass Spectrom 38:283–295

    Article  CAS  Google Scholar 

  7. Kratzsch C, Tenberken O, Peters FT, Weber AA, Kraemer T, Maurer HH (2004) J Mass Spectrom 39:856–872

    Article  CAS  Google Scholar 

  8. Lee HK, Ho CS, Iu YP, Lai PS, Shek CC, Lo YC, Klinke HB, Wood M (2009) Anal Chim Acta 649:80–90

    Article  CAS  Google Scholar 

  9. Fitzgerald RL, Rivera JD, Herold DA (1999) Clin Chem 45:1224–1234

    CAS  Google Scholar 

  10. Sauvage FL, Gaulier JM, Lachatre G, Marquet P (2006) Ther Drug Monit 28:123–130

    Article  CAS  Google Scholar 

  11. Decaestecker TN, Clauwaert KM, Van Bocxlaer JF, Lambert WE, Van den Eeckhout EG, Van Peteghem CH, De Leenheer AP (2000) Rapid Commun Mass Spectrom 14:1787–1792

    Article  CAS  Google Scholar 

  12. Baumann C, Cintora MA, Eichler M, Lifante E, Cooke M, Przyborowska A, Halket JM (2000) Rapid Commun Mass Spectrom 14:349–356

    Article  CAS  Google Scholar 

  13. Marquet P, Saint-Marcoux F, Gamble TN, Leblanc JC (2003) J Chromatogr B Analyt Technol Biomed Life Sci 789:9–18

    Article  CAS  Google Scholar 

  14. Decaestecker TN, Vande C Sr, Wallemacq PE, Van Peteghem CH, Defore DL, Van Bocxlaer JF (2004) Anal Chem 76:6365–6373

    Article  CAS  Google Scholar 

  15. Pavlic M, Libiseller K, Oberacher H (2006) Anal Bioanal Chem 386:69–82

    Article  CAS  Google Scholar 

  16. Josephs JL, Sanders M (2004) Rapid Commun Mass Spectrom 18:743–759

    Article  CAS  Google Scholar 

  17. Mueller CA, Weinmann W, Dresen S, Schreiber A, Gergov M (2005) Rapid Commun Mass Spectrom 19:1332–1338

    Article  CAS  Google Scholar 

  18. Sauvage FL, Saint-Marcous F, Duretz B, Deporte D, Lachatre G, Marquet P (2006) Clin Chem 52:1735–1742

    Article  CAS  Google Scholar 

  19. Dresen S, Gergov M, Politi L, Halter C, Weinmann W (2009) Anal Bioanal Chem 395:2521–2526

    Article  CAS  Google Scholar 

  20. Sauvage FL, Picard N, Saint-Marcoux F, Gaulier JM, Lachatre G, Marquet P (2009) J Sep Sci 32:3074–3083

    Article  CAS  Google Scholar 

  21. Dulaurent S, Moesch C, Marquet P, Gaulier JM, Lachatre G (2010) Anal Bioanal Chem 396:2235–2249

    Article  CAS  Google Scholar 

  22. Liu HC, Liu RH, Lin DL, Ho HO (2010) Rapid Commun Mass Spectrom 24:75–84

    Article  Google Scholar 

  23. Picard N, Dridi D, Sauvage FL, Boughattas NA, Marquet P (2009) J Sep Sci 32:2209–2217

    Article  CAS  Google Scholar 

  24. Sturm S, Hammann F, Drewe J, Maurer HH, Scholer A (2010) J Chromatogr B 878:2726–2732

    Article  CAS  Google Scholar 

  25. Baselt RC (2009) Disposition of toxic drugs and chemicals in man. Biomedical Publications, Foster City

    Google Scholar 

  26. Lynch KL, Breaud AR, Vandenberghe H, Wu AH, Clarke W (2010) Clin Chim Acta 411:1474–1481

    Article  CAS  Google Scholar 

  27. Hopley C, Bristow T, Lubben A, Simpson A, Bull E, Klagkou K, Herniman J, Langley J (2008) Rapid Commun Mass Spectrom 22:1779–1786

    Article  CAS  Google Scholar 

  28. Philipp AA, Wissenbach DK, Zoerntlein SW, Klein ON, Kanogsunthornrat J, Maurer HH (2009) J Mass Spectrom 44:1249–1261

    Article  CAS  Google Scholar 

  29. Maurer HH, Pfleger K, Weber AA (2007) Mass spectral library of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim

    Google Scholar 

  30. Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Anal Chem 75:3019–3030

    Article  CAS  Google Scholar 

  31. Philipp AA, Wissenbach DK, Weber AA, Zapp J, Zoerntlein SW, Klein ON, Kanogsunthornrat J, Maurer HH (2010) Anal Bioanal Chem 396:2379–2391

    Article  CAS  Google Scholar 

  32. Philipp AA, Wissenbach DK, Weber AA, Zapp J, Maurer HH (2010) J Mass Spectrom, in press

  33. Maurer H, Pfleger K (1984) J Chromatogr 305:309–323

    Article  CAS  Google Scholar 

  34. Maurer HH, Bickeboeller-Friedrich J (2000) J Anal Toxicol 24:340–347

    CAS  Google Scholar 

  35. Meyer MR, Maurer HH (2010) Curr Drug Metab 11:468–482

    Article  CAS  Google Scholar 

  36. Schwaninger AE, Meyer MR, Maurer HH (2010) J Anal Toxicol 34:45–48

    CAS  Google Scholar 

  37. Oberacher H, Pavlic M, Libiseller K, Schubert B, Sulyok M, Schuhmacher R, Csaszar E, Kofeler HC (2009) J Mass Spectrom 44:485–493

    Article  CAS  Google Scholar 

  38. Oberacher H, Pavlic M, Libiseller K, Schubert B, Sulyok M, Schuhmacher R, Csaszar E, Kofeler HC (2009) J Mass Spectrom 44:494–502

    Article  CAS  Google Scholar 

  39. Mylonas R, Mauron Y, Masselot A, Binz PA, Budin N, Fathi M, Viette V, Hochstrasser DF, Lisacek F (2009) Anal Chem 81:7604–7610

    Article  CAS  Google Scholar 

  40. Li AC, Gohdes MA, Shou WZ (2007) Rapid Commun Mass Spectrom 21:1421–1430

    Article  CAS  Google Scholar 

  41. Rivier L (2003) Anal Chim Acta 492:69–82

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Benjamin Honold, Golo M. Meyer, Peter Niklas, Frank T. Peters, Anika-Anina Philipp, Andrea E. Schwaninger, Carsten Schröder, Gabi Ulrich and Lydia Zweigler as well as Kornelia Weidemann and Edeltraud Thiry (ThermoFisher Scientific Instruments, Dreieich, Germany), and Pierre-Alain Binz, Nicolas Budin, Yann Mauron, and Roman Mylonas (GeneBio, Geneva, Switzerland) for their support.

Author information

Authors and Affiliations

  1. Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, 66421, Homburg, Saar, Germany

    Dirk K. Wissenbach, Markus R. Meyer, Daniela Remane, Armin A. Weber & Hans H. Maurer

Authors
  1. Dirk K. Wissenbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Markus R. Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Remane
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Armin A. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hans H. Maurer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hans H. Maurer.

Additional information

Published in the special issue Forensic Toxicology with Guest Editors Frank T. Peters, Hans H. Maurer, and Frank Musshoff.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 177 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wissenbach, D.K., Meyer, M.R., Remane, D. et al. Development of the first metabolite-based LC-MSn urine drug screening procedure-exemplified for antidepressants. Anal Bioanal Chem 400, 79–88 (2011). https://doi.org/10.1007/s00216-010-4398-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-010-4398-9

Keywords

Search

Navigation