Skip to main content

Advertisement

SpringerLink
Log in

Current role of liquid chromatography–mass spectrometry in clinical and forensic toxicology

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

This paper reviews multi-analyte single-stage and tandem liquid chromatography–mass spectrometry (LC-MS) procedures using different mass analyzers (quadrupole, ion trap, time-of-flight) for screening, identification, and/or quantification of drugs, poisons, and/or their metabolites in blood, plasma, serum, or urine published after 2004. Basic information about the biosample assayed, work-up, LC column, mobile phase, ionization type, mass spectral detection mode, and validation data of each procedure is summarized in tables. The following analytes are covered: drugs of abuse, analgesics, opioids, sedative-hypnotics, benzodiazepines, antidepressants including selective-serotonin reuptake inhibitors (SSRIs), herbal phenalkylamines (ephedrines), oral antidiabetics, antiarrhythmics and other cardiovascular drugs, antiretroviral drugs, toxic alkaloids, quaternary ammonium drugs and herbicides, and dialkylphosphate pesticides. The pros and cons of the reviewed procedures are critically discussed, particularly, the need for studies on matrix effects, selectivity, analyte stability, and the use of stable-isotope labeled internal standards instead of unlabeled therapeutic drugs. In conclusion, LC-MS will probably become a gold standard for detection of very low concentrations particularly in alternative matrices and for quantification in clinical and forensic toxicology. However, some drawbacks still need to be addressed and finally overcome.

Photos of LC-MS apparatus and typical samples suitable for toxicological analysis

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

Similar content being viewed by others

References

  1. Maurer HH (2006) J Mass Spectrom 41:1399–1413

    Article  CAS  Google Scholar 

  2. Maurer HH (1992) J Chromatogr 580:3–41

    Article  CAS  Google Scholar 

  3. Maurer HH (2004) Clin Chem Lab Med 42:1310–1324

    Article  CAS  Google Scholar 

  4. Hoja H, Marquet P, Verneuil B, Lotfi H, Penicaut B, Lachatre G (1997) J Anal Toxicol 21:116–126

    CAS  Google Scholar 

  5. Maurer HH (1998) J Chromatogr B Biomed Sci Appl 713:3–25

    Article  CAS  Google Scholar 

  6. Peters FT (2006) Method Validation using LC-MS. In: Polettini A (ed) Applications of liquid chromatography-mass spectrometry in toxicology. Pharmaceutical Press, London, pp 71–95

    Google Scholar 

  7. Maurer HH (2005) Clin Biochem 38:310–318

    Article  CAS  Google Scholar 

  8. Maurer HH (2005) Anal Bioanal Chem 381:110–118

    Article  CAS  Google Scholar 

  9. Wood M, Laloup M, Samyn N, Mar Ramirez FM, De Bruijn EA, Maes RA, de Boeck G (2006) J Chromatogr A 1130:3–15

    Article  CAS  Google Scholar 

  10. Kintz P (2007) Anal Bioanal Chem (in press)

  11. Politi L, Leone F, Morini L, Polettini A (2007) Anal Bioanal Chem (in press)

  12. Dams R, Huestis MA, Lambert WE, Murphy CM (2003) J Am Soc Mass Spectrom 14:1290–1294

    Article  CAS  Google Scholar 

  13. Beyer J, Peters FT, Kraemer T, Maurer HH (2007) J Mass Spectrom 42:Feb 26 [Epub ahead of print]

  14. Maurer HH (2007) Forensic Sci Int 165:194–198

    Article  Google Scholar 

  15. Van Bocxlaer JF, Clauwaert KM, Lambert WE, Deforce DL, Van den Eeckhout EG, de-Leenheer AP (2000) Mass Spectrom Rev 19:165–214

    Article  Google Scholar 

  16. Marquet P (2002) Ther Drug Monit 24:255–276

    Article  CAS  Google Scholar 

  17. Hernandez F, Sancho JV, Pozo OJ (2005) Anal Bioanal Chem 382:934–946

    Google Scholar 

  18. Maurer HH (2005) Ann Toxicol Anal 17:13–20

    Google Scholar 

  19. Kraemer T, Paul LD (2007) Anal Bioanal Chem (in press)

  20. Drummer OH (2007) Anal Bioanal Chem (in press)

  21. Huestis M (2007) Anal Bioanal Chem (in press)

  22. Musshoff F, Madea B (2007) Anal Bioanal Chem (in press)

  23. Samyn N, Laloup M, de Boeck G (2007) Anal Bioanal Chem (in press)

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  26. Maurer HH, Peters FT (2006) Analysis of therapeutic drugs with LC-MS. In: Polettini A (ed) Applications of liquid chromatography-mass spectrometry in toxicology. Pharmaceutical Press, London, pp 131–147

    Google Scholar 

  27. Maurer HH, Peters FT (2005) Ther Drug Monit 27:686–688

    Article  CAS  Google Scholar 

  28. Maurer HH, Peters FT (2006) Analyte identification using library searching in GC-MS and LC-MS. In: Gross M, Caprioli RM (eds) Encyclopedia of mass spectrometry. Elsevier, Oxford, pp 115–121

    Google Scholar 

  29. Marquet P (2002) Ther Drug Monit 24:125–133

    Article  CAS  Google Scholar 

  30. Peters FT, Drummer OH, Musshoff F (2007) Forensic Sci Int 165:216–224

    Article  CAS  Google Scholar 

  31. Lindner W, Wainer IW (1998) J Chromatogr B 707:1–2

    Article  CAS  Google Scholar 

  32. Miyaguchi H, Kuwayama K, Tsujikawa K, Kanamori T, Iwata YT, Inoue H, Kishi T (2006) Forensic Sci Int 157:57–70

    Article  CAS  Google Scholar 

  33. Maurer HH, Pfleger K, Weber AA (2007) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites, 3rd edn, part 1. Wiley-VCH, Weinheim, pp 3–201

  34. Saint-Marcoux F, Lachatre G, Marquet P (2003) J Am Soc Mass Spectrom 14:14–22

    Article  CAS  Google Scholar 

  35. Maurer HH (2007) Forensic screening with GC-MS. In: Bogusz M (ed) Handbook of analytical separation sciences: forensic sciences, 2nd edn. Elsevier, Amsterdam (in press)

  36. Gergov M, Boucher B, Ojanpera I, Vuori E (2001) Rapid Commun Mass Spectrom 15:521–526

    Article  CAS  Google Scholar 

  37. Pelander A, Ojanpera I, Laks S, Rasanen I, Vuori E (2003) Anal Chem 75:5710–5718

    Article  CAS  Google Scholar 

  38. Ojanpera I, Pelander A, Laks S, Gergov M, Vuori E, Witt M (2005) J Anal Toxicol 29:34–40

    Google Scholar 

  39. Ojanpera S, Pelander A, Pelzing M, Krebs I, Vuori E, Ojanpera I (2006) Rapid Commun Mass Spectrom 20:1161–1167

    Article  CAS  Google Scholar 

  40. Pfleger K, Maurer HH, Weber A (1992) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites, 2nd edn. VCH, Weinheim

    Google Scholar 

  41. Nordgren HK, Beck O (2003) J Anal Toxicol 27:15–19

    CAS  Google Scholar 

  42. Nordgren HK, Beck O (2004) Ther Drug Monit 26:90–97

    Article  CAS  Google Scholar 

  43. Nordgren HK, Holmgren P, Liljeberg P, Eriksson N, Beck O (2005) J Anal Toxicol 29:234–239

    CAS  Google Scholar 

  44. Gustavsson E, Andersson M, Stephanson N, Beck O (2007) J Mass Spectrom 42 (in press)

  45. Cheng WC, Yau TS, Wong MK, Chan LP, Mok VK (2006) Forensic Sci Int 162:95–107

    Article  CAS  Google Scholar 

  46. Wu TY, Fuh MR (2005) Rapid Commun Mass Spectrom 19:775–780

    Article  CAS  Google Scholar 

  47. Quintela O, Sauvage FL, Charvier F, Gaulier JM, Lachatre G, Marquet P (2006) Clin Chem 52:1346–1355

    Article  CAS  Google Scholar 

  48. ElSohly MA, Gul W, ElSohly KM, Avula B, Khan IA (2006) J Anal Toxicol 30:524–538

    CAS  Google Scholar 

  49. Thevis M, Geyer H, Bahr D, Schanzer W (2005) Eur J Mass Spectrom (Chichester, Eng) 11:419–427

    Article  CAS  Google Scholar 

  50. Thevis M, Geyer H, Schanzer W (2005) Rapid Commun Mass Spectrom 19:928–936

    Article  CAS  Google Scholar 

  51. Dulaurent S, Saint-Marcoux F, Marquet P, Lachatre G (2006) J Chromatogr B Anal Technol Biomed Life Sci 831:223–229

    Article  CAS  Google Scholar 

  52. Allen KR (2006) Clin Toxicol (Phila) 44:147–153

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  54. Peters FT, Jung J, Kraemer T, Maurer HH (2005) Ther Drug Monit 27:334–344

    Article  CAS  Google Scholar 

  55. Juan H, Zhiling Z, Huande L (2005) J Chromatogr B Anal Technol Biomed Life Sci 820:33–39

    Article  CAS  Google Scholar 

  56. Quintela O, Cruz A, Castro A, Concheiro M, Lopez-Rivadulla M (2005) J Chromatogr B Anal Technol Biomed Life Sci 825:63–71

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  58. Laloup M, Ramirez Fernandez MM, de Boeck G, Wood M, Maes V, Samyn N (2005) J Anal Toxicol 29:616–626

    CAS  Google Scholar 

  59. Smink BE, Brandsma JE, Dijkhuizen A, Lusthof KJ, de Gier JJ, Egberts AC, Uges DR (2004) J Chromatogr B Anal Technol Biomed Life Sci 811:13–20

    Article  CAS  Google Scholar 

  60. Bugey A, Rudaz S, Staub C (2006) J Chromatogr B Anal Technol Biomed Life Sci 832:249–255

    Article  CAS  Google Scholar 

  61. Beyer J, Peters FT, Kraemer T, Maurer HH (2007) J Mass Spectrom 42:150–160

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  63. Maurer HH, Kratzsch C, Kraemer T, Peters FT, Weber AA (2002) J Chromatogr B Anal Technol Biomed Life Sci 773:63–73

    Article  CAS  Google Scholar 

  64. Maurer HH, Tenberken O, Kratzsch C, Weber AA, Peters FT (2004) J Chromatogr A 1058:169–181

    Article  CAS  Google Scholar 

  65. Musshoff F, Trafkowski J, Kuepper U, Madea B (2006) J Mass Spectrom 41:633–640

    Article  CAS  Google Scholar 

  66. Hori Y, Fujisawa M, Shimada K, Hirose Y, Yoshioka T (2006) Biol Pharm Bull 29:7–13

    Article  CAS  Google Scholar 

  67. Li S, Liu G, Jia J, Liu Y, Pan C, Yu C, Cai Y, Ren J (2007) J Chromatogr B Anal Technol Biomed Life Sci [Epub ahead of print]

  68. Kristoffersen L, Oiestad EL, Opdal MS, Krogh M, Lundanes E, Christophersen AS (2007) J Chromatogr B Anal Technol Biomed Life Sci [Epub ahead of print]

  69. Maurer HH, Sauer C, Theobald DS (2006) Ther Drug Monit 28:447–453

    Article  CAS  Google Scholar 

  70. Antoniou T, Tseng AL (2002) Ann Pharmacother 36:1598–1613

    Article  CAS  Google Scholar 

  71. Dickinson L, Robinson L, Tjia J, Khoo S, Back D (2005) J Chromatogr B Anal Technol Biomed Life Sci 829:82–90

    Article  CAS  Google Scholar 

  72. Koal T, Burhenne H, Romling R, Svoboda M, Resch K, Kaever V (2005) Rapid Commun Mass Spectrom 19:2995–3001

    Article  CAS  Google Scholar 

  73. van den Broek I, Sparidans RW, Huitema AD, Schellens JH, Beijnen JH (2006) J Chromatogr B Anal Technol Biomed Life Sci 837:49–58

    Article  CAS  Google Scholar 

  74. Ariffin MM, Anderson RA (2006) J Chromatogr B Anal Technol Biomed Life Sci 842:91–97

    Article  CAS  Google Scholar 

  75. Annesley TM (2003) Clin Chem 49:1041–1044

    Article  CAS  Google Scholar 

  76. King R, Bonfiglio R, Fernandez-Metzler C, Miller-Stein C, Olah T (2000) J Am Soc Mass Spectrom 11:942–950

    Article  CAS  Google Scholar 

  77. Liang HR, Foltz RL, Meng M, Bennett P (2003) Rapid Commun Mass Spectrom 17:2815–2821

    Article  CAS  Google Scholar 

  78. Mallet CR, Lu Z, Mazzeo JR (2004) Rapid Commun Mass Spectrom 18:49–58

    Article  CAS  Google Scholar 

  79. Matuszewski BK, Constanzer ML, Chavez EC (1998) Anal Chem 70:882–889

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  81. Matuszewski BK (2006) J Chromatogr B Anal Technol Biomed Life Sci 830:293–300

    Article  CAS  Google Scholar 

  82. Muller C, Schafer P, Stortzel M, Vogt S, Weinmann W (2002) J Chromatogr B Anal Technol Biomed Life Sci 773:47–52

    Article  CAS  Google Scholar 

  83. Niessen WM, Manini P, Andreoli R (2006) Mass Spectrom Rev 25:881–899

    Article  CAS  Google Scholar 

  84. Schuhmacher J, Zimmer D, Tesche F, Pickard V (2003) Rapid Commun Mass Spectrom 17:1950–1957

    Article  CAS  Google Scholar 

  85. Souverain S, Rudaz S, Veuthey J-L (2004) J Chromatogr A 1058:61–66

    Article  CAS  Google Scholar 

  86. Taylor PJ (2005) Clin Biochem 38:328–334

    Article  CAS  Google Scholar 

  87. Peters FT (2007) Anal Bioanal Chem (in press)

Download references

Acknowledgements

The author would like to thank Dr. Frank T. Peters, Dr. Jochen Beyer, Melanie Mueller, and Andreas H. Ewald for their suggestions and help.

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

    Hans H. Maurer

Authors
  1. Hans H. Maurer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hans H. Maurer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maurer, H.H. Current role of liquid chromatography–mass spectrometry in clinical and forensic toxicology. Anal Bioanal Chem 388, 1315–1325 (2007). https://doi.org/10.1007/s00216-007-1248-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-007-1248-5

Keywords

Search

Navigation