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Fast screening of 88 pharmaceutical drugs and metabolites in whole blood by ultrahigh-performance liquid chromatography–tandem mass spectrometry

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Abstract

Forensic investigations involving acute or lethal intoxication, drug-facilitated sexual assault, driving or workplace impairment frequently require the analysis of fresh or postmortem blood samples to check out a wide variety of pharmaceutical and illicit drugs, even after single-dose consumption. A sensitive and selective ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) screening method was developed for fast screening of 88 psychoactive drugs and metabolites in blood samples, including the ones most frequently involved in acute intoxications and forensic investigations in Italy. The new method allows short sample processing and analysis time (the whole procedure can be accomplished in less than 30 min) together with the simultaneous monitoring of a large number of pharmaceutical substances. These features represent crucial factors in the approach of acute intoxications, when the patient requires urgent and appropriate therapy. Blood sample treatment was limited to protein precipitation. Two UHPLC–MS/MS runs in positive and negative electrospray ionization modes were performed. The data were acquired at unit mass resolution in the selected reaction monitoring mode. According to international guidelines, linearity range, precision, trueness, detection and quantification limits, recovery, selectivity, specificity, carryover, and matrix effect phenomena were determined. Despite the limited sample purification and the inherent decreased chance of eliminating any potential interference, the present multiresidue screening method proved extremely effective and sensitive, allowing the detection of all tested drugs, even those belonging to structurally different classes of substances. Moreover, the developed method is easily susceptible to further expansion to encompass more drugs, either new or those becoming important for criminal investigation. This protocol was also applied to the analysis of authentic blood samples collected from victims of various crimes in routine casework, whose relevance in forensic investigations is presented in five cases.

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References

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

    Article  CAS  Google Scholar 

  2. Levine B (2006) Principles of forensic toxicology, 2nd edn. American Association for Clinical Chemistry, Washington, DC

    Google Scholar 

  3. Karch SB (2008) Postmortem toxicology of abused drugs. CRC Press, Boca Raton

    Google Scholar 

  4. Maurer HH (2009) Anal Bioanal Chem 393:97–107

    Article  CAS  Google Scholar 

  5. Couchman L, Morgan PE (2011) Biomed Chromatogr 25:100–123

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Arroyo A, Sánchez M, Palahí M, Barbal M, Marrón MA, Mora A (2011) Led Med (Tokyo) 13:240–244

    Article  Google Scholar 

  8. Johnson RD, Botch SR (2011) J Anal Toxicol 35:65–74

    Article  CAS  Google Scholar 

  9. Drummer OH, Kourtis I, Beyer J, Tayler P, Boorman M, Gerostamoulos D (2012) Forensic Sci Int 215:14–17

    Article  CAS  Google Scholar 

  10. Wissenbach DK, Meyer MR, Remane D, Philipp AA, Weber AA, Maurer HH (2011) Anal Bioanal Chem 400:3481–3489

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Herrin GL, Horton McCurdy H, Wall WH (2005) J Anal Toxicol 29:599–606

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Moeller MR, Steinmeyer S, Kraemer T (1998) J Chromatogr B: Biomed Sci Appl 713:91–109

    Article  CAS  Google Scholar 

  16. Choe S, Kim S, Choi H, Choi H, Chung H, Hwang B (2010) Forensic Sci Int 199:50–57

    Article  CAS  Google Scholar 

  17. Song SM, Marriott P, Wynne P (2004) J Chromatogr A 1058(1–2):223–232

    CAS  Google Scholar 

  18. Sporkert F, Brunel C, Augsburger MP, Mangin P (2012) Forensic Sci Int 215:101–104

    Article  CAS  Google Scholar 

  19. Bjørk MK, Nielsen MKK, Markussen LØ, Klinke HB, Linnet K (2010) Anal Bioanal Chem 396:2393–2401

    Article  Google Scholar 

  20. Wohlfarth A, Weinmann W, Dresen S (2010) Anal Bioanal Chem 396:2403–2414

    Article  CAS  Google Scholar 

  21. Sergi M, Bafile E, Compagnone D, Curini R, D’Ascenzo G, Romolo FS (2009) Anal Bioanal Chem 393:709–718

    Article  CAS  Google Scholar 

  22. Bassan DM, Erdmann F, Krüll R (2011) Anal Bioanal Chem 400:43–50

    Article  CAS  Google Scholar 

  23. Dresen S, Ferreirós N, Gnann H, Zimmermann R, Weinmann W (2010) Anal Bioanal Chem 396:2425–2434

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  25. Broecker S, Herre S, Wüst B, Zweigenbaum J, Pragst F (2011) Anal Bioanal Chem 400:101–117

    Article  CAS  Google Scholar 

  26. Remane D, Meyer MR, Wissenbach DK, Maurer HH (2011) Anal Bioanal Chem 401:1341–1352

    Article  CAS  Google Scholar 

  27. Remane D, Meyer MR, Peters FT, Wissenbach DK, Maurer HH (2010) Anal Bioanal Chem 397:2303–2314

    Article  CAS  Google Scholar 

  28. Remane D, Meyer MR, Wissenbach DK, Maurer HH (2011) Anal Bioanal Chem 400:2093–2107

    Article  CAS  Google Scholar 

  29. Rosano TG, Wood M, Swift TA (2011) J Anal Toxicol 35:411–423

    Article  CAS  Google Scholar 

  30. Heinig K, Wirz T, Bucheli F, Monin V, Gloge A (2011) J Pharm Biomed Anal 54:742–749

    Article  CAS  Google Scholar 

  31. Soriano T, Jurado C, Menéndez M, Repetto M (2001) J Anal Toxicol 25:137–143

    CAS  Google Scholar 

  32. Wille SMR, Lambert WEE (2007) Anal Bioanal Chem 388:1381–1391

    Article  CAS  Google Scholar 

  33. Baselt RC (2004) Disposition of toxic drugs and chemicals in man, 7th edn. Biomedical Publications, Foster City

    Google Scholar 

  34. Clarke EGC (2005) Clarke’s isolation and identification of drugs in pharmaceutical, body fluids and post-mortem materials, 3rd edn. The Pharmaceutical Press, London

    Google Scholar 

  35. TIAFT (2004) TIAFT reference blood level list of therapeutic and toxic substances. http://www.tiaft.org/toxic_values. Accessed 4 Jun 2012

  36. GTFI (2010) Linee guida per i laboratori di analisi di sostanze d’abuso con finalità tossicologico-forensi e medico-legali. Gruppo Tossicologi Forensi Italiani, Pavia

    Google Scholar 

  37. EC (2002) Commission Decision 2002/657/EC of 12 August 2002 implementing Council Directive 96/23/EC concerning the performance of analytical methods and the interpretation of results. Off J Eur Commun L221/8–36

    Google Scholar 

  38. DIN 32645 (1994) Chemical analysis, decision limit, detection limit, and determination limit: estimation in case of repeatability, terms, methods, evaluation. Beuth Verlag, Berlin

  39. SOFT/AAFS (2006) Forensic toxicology laboratory guidelines. Society of Forensic Toxicologists/American Academy of Forensic Sciences. http://www.soft-tox.org/files/Guidelines_2006_Final.pdf. Accessed 4 Jun 2012

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

    Article  CAS  Google Scholar 

  41. Chambers E, Wagrowski-Diehl DM, Lu Z, Mazzeo JR (2007) J Chromatogr B 852:22–34

    Article  CAS  Google Scholar 

  42. Remane D, Meyer MR, Wissenbach DK, Maurer HH (2010) Rapid Commun Mass Spectrom 24:3103–3108

    Google Scholar 

  43. Eeckhaut AV, Lanckmans K, Sarre S, Smolders I, Michotte Y (2009) J Chromatogr B Anal Technol Biomed Life Sci 877:2198–2207

    Article  Google Scholar 

  44. Salomone A, Di Corcia D, Gerace E, Vincenti M (2011) J Anal Toxicol 35:519–523

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Dr. Sergio Pellegrino for his keen cooperation and the laboratory personnel for preparing the samples. The generous financial contribution for renovating analytical instrumentation from the Compagnia di San Paolo (Turin, Italy) is gratefully acknowledged (Grant 411/PV-2009.1993). The authors are also indebted to the Regione Piemonte for its continuous financial support.

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Correspondence to Alberto Salomone.

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Published in the special issue Analytical Science in Italy with guest editor Aldo Roda.

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Vincenti, M., Cavanna, D., Gerace, E. et al. Fast screening of 88 pharmaceutical drugs and metabolites in whole blood by ultrahigh-performance liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 405, 863–879 (2013). https://doi.org/10.1007/s00216-012-6403-y

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  • DOI: https://doi.org/10.1007/s00216-012-6403-y

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