Advertisement

Determination of antipsychotic drugs in oral fluid using dried saliva spots by gas chromatography-tandem mass spectrometry

  • Débora Caramelo
  • Tiago Rosado
  • Victor Oliveira
  • Jesus M. Rodilla
  • Pedro M. M. Rocha
  • Mário Barroso
  • Eugenia GallardoEmail author
Research Paper

Abstract

The present work describes the optimization and validation of an analytical method for the determination of six antipsychotic drugs (chlorpromazine, levomepromazine, cyamemazine, clozapine, haloperidol, and quetiapine) in oral fluid samples after solvent extraction from dried saliva spots, by gas chromatography coupled to tandem mass spectrometry. The method was fully validated, and the included parameters were selectivity, linearity, limits of quantification, precision and accuracy, stability, and recovery. The method was linear for all compounds from 10 to 400 ng/mL, except for haloperidol (5–100 ng/mL), presenting coefficients of determination higher than 0.99. Inter- and intra-day precision and accuracy were in conformity with the criteria usually seen in bioanalytical method validation; i.e., coefficients of variation were lower than 15% and an accuracy of 15% or better for all studied drugs. The recoveries obtained with this miniaturized technique ranged from 63 to 97%. The herein described method is the first to be reported using the dried saliva spots approach for the analysis of these antypshychotic drugs, proving great sensitivity apart from its simple and fast procedure. The method was considered a good alternative to the conventional techniques to be applied in clinical and toxicological analyses, even more taking into account the extremely low sample volume used (50 μL).

Graphical abstract

Keywords

Dried saliva spots Oral fluid GC-MS/MS Antipsychotic drugs 

Notes

Acknowledgments

The authors acknowledge all the nursing team of the Departamento de Psiquiatria e Saúde Mental from the Centro Hospitalar Cova da Beira.

Funding information

This work is supported by FEDER funds through the POCI-COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I – Strengthening Research, Technological Development and Innovation (Project POCI-01- 0145-FEDER-007491) and National Funds by FCT – Foundation for Science and Technology (UID / Multi / 00709/2019).

Compliance with ethical standards

The present study was approved by the ethics committee from Centro Hospitalar Cova da Beira and has been conducted according to ethical standards. The analyzed authentic samples belonged to individuals who provided an informed consent for their use, and all analyses were carried out according to the ethical standards of the institution.

Conflict of interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Mcguire P, Howes OD, Stone J, Fusar-poli P. Functional neuroimaging in schizophrenia: diagnosis and drug discovery. Trends Pharmacol Sci. 2008;29:91–8.  https://doi.org/10.1016/j.tips.2007.11.005.CrossRefGoogle Scholar
  2. 2.
    Mohammadi M, Akhondzadeh S. Schizophrenia: etiology and pharmacotherapy. IDrugs. 2001;4:1167–72.Google Scholar
  3. 3.
    Da Fonseca BM, Moreno IED, Barroso M, Costa S, Queiroz JA, Gallardo E. Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography – tandem mass spectrometry. Anal Bioanal Chem. 2013;405:3953–63.  https://doi.org/10.1007/s00216-012-6695-y.CrossRefGoogle Scholar
  4. 4.
    Miyamoto S, Duncan GE, Marx CE, Lieberman JA. Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry. 2005;10:79–104.  https://doi.org/10.1038/sj.mp.4001556.CrossRefGoogle Scholar
  5. 5.
    Freedman R. Schizophrenia. N Engl J Med. 2003;349:1738–49.CrossRefGoogle Scholar
  6. 6.
    Huestis MA, Verstraete A, Kwong TC, Morland J, Vincent MJ, de la Torre R. Oral fluid testing: promises and pitfalls. Clin Chem. 2011;57:805–10.CrossRefGoogle Scholar
  7. 7.
    Gallardo E, Barroso M, Queiroz JA. Current technologies and considerations for drug bioanalysis in oral fluid. Bioanalysis. 2009;1:637–67.  https://doi.org/10.4155/bio.09.23.CrossRefGoogle Scholar
  8. 8.
    Gallardo E, Queiroz JA. The role of alternative specimens in toxicological analysis. Biomed Chromatogr. 2008;22:795–821.  https://doi.org/10.1002/bmc.1009.CrossRefGoogle Scholar
  9. 9.
    Petruczynik A, Wróblewski K, Szultka-Młyńska M, Buszewski B, Karakuła-Juchnowicz H, Gajewski J, et al. Determination of some psychotropic drugs in serum and saliva samples by HPLC-DAD and HPLC MS. J Pharm Biomed Anal. 2016;127:68–80.  https://doi.org/10.1016/j.jpba.2016.01.004.CrossRefGoogle Scholar
  10. 10.
    Fisher DS, Partridge SJ, Handley SA, Couchman L, Morgan PE, Flanagan RJ. LC–MS/MS of some atypical antipsychotics in human plasma, serum, oral fluid and haemolysed whole blood. Forensic Sci Int. 2013;229:145–50.  https://doi.org/10.1016/j.forsciint.2013.02.010.CrossRefGoogle Scholar
  11. 11.
    Patteet L, Maudens KE, Morrens M, Sabbe B, Dom G, Neels H. Determination of common antipsychotics in quantisal-collected oral fluid by UHPLC-MS/MS: method validation and applicability for therapeutic drug monitoring. Ther Drug Monit. 2016;38:87–97.  https://doi.org/10.1097/FTD.0000000000000242.CrossRefGoogle Scholar
  12. 12.
    Di Corcia D, Lisi S, Pirro V, Gerace E, Salomone A, Vincenti M. Determination of pharmaceutical and illicit drugs in oral fluid by ultra-high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B. 2013;927:133–41.  https://doi.org/10.1016/j.jchromb.2013.01.025.CrossRefGoogle Scholar
  13. 13.
    Saracino MA, De Palma A, Boncompagni G, Raggi MA. Analysis of risperidone and its metabolite in plasma and saliva by LC with coulometric detection and a novel MEPS procedure. Talanta. 2010;81:1547–53.  https://doi.org/10.1016/j.talanta.2010.02.067.CrossRefGoogle Scholar
  14. 14.
    Elmongy H, Abdel-Rehim M. Saliva as an alternative specimen to plasma for drug bioanalysis: a review. Trends Anal Chem. 2016;83:70–9.  https://doi.org/10.1016/j.trac.2016.07.010.CrossRefGoogle Scholar
  15. 15.
    Neumann J, Beck O, Dahmen N, Böttcher M. Potential of oral fluid as a clinical specimen for compliance monitoring of psychopharmacotherapy. Ther Drug Monit. 2018;40:245–51.CrossRefGoogle Scholar
  16. 16.
    Abu-Rabie P, Spooner N. Dried matrix spot direct analysis: evaluating the robustness of a direct elution technique for use in quantitative bioanalysis. Bioanalysis. 2011;3:2769–81.  https://doi.org/10.4155/bio.11.270.CrossRefGoogle Scholar
  17. 17.
    Abdel-Rehim A, Abdel-Rehim M. Dried saliva spot as a sampling technique for saliva samples. Biomed Chromatogr. 2014;28:875–7.  https://doi.org/10.1002/bmc.3193.CrossRefGoogle Scholar
  18. 18.
    Carvalho J, Rosado T, Barroso M, Gallardo E, Investigação C De, Interior B, D AI, Fármaco-toxicologia L De, Beira U. Determination of antiepileptic drugs using dried saliva spots. J Anal Toxicol. 2018:1–11.  https://doi.org/10.1093/jat/bky064.
  19. 19.
    Ribeiro A, Prata M, Vaz C, Rosado T, Restolho J, Barroso M, et al. Determination of methadone and EDDP in oral fluid using the dried saliva spots sampling approach and gas chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2019:1–11.  https://doi.org/10.1007/s00216-019-01654-z.
  20. 20.
    Numako M, Takayama T, Noge I, Kitagawa Y, Todoroki K, et al. Dried saliva spot (DSS) as a convenient and reliable sampling for bioanalysis: an application for the diagnosis of diabetes mellitus. Anal Chem. 2015;88:635–9.  https://doi.org/10.1021/acs.analchem.5b04059.CrossRefGoogle Scholar
  21. 21.
    Chen X, Zheng S, Le J, Qian Z, Zhang R, Hong Z, et al. Ultrasound-assisted low-density solvent dispersive liquid–liquid microextraction for the simultaneous determination of 12 new antidepressants and 2 antipsychotics in whole blood by gas chromatography–mass spectrometry. J Pharm Biomed Anal. 2017;142:19–27.  https://doi.org/10.1016/j.jpba.2017.04.032.CrossRefGoogle Scholar
  22. 22.
    Rosado T, Oppolzer D, Cruz B, Barroso M, Varela S, Oliveira V, et al. Development and validation of a gas chromatography/tandem mass spectrometry method for simultaneous quantitation of several antipsychotics in human plasma and oral fluid. Rapid Commun Mass Spectrom. 2018;32:2081–95.  https://doi.org/10.1002/rcm.8087.CrossRefGoogle Scholar
  23. 23.
    Koller D, Zubiaur P, Saiz-Rodríguez M, Abad-Santos F, Wojnicz A. Simultaneous determination of six antipsychotics, two of their metabolites and caffeine in human plasma by LC-MS/MS using a phospholipid-removal microelution-solid phase extraction method for sample preparation. Talanta. 2019;198:159–68.  https://doi.org/10.1016/j.talanta.2019.01.112.CrossRefGoogle Scholar
  24. 24.
    Patteet L, Cappelle D, Maudens KE, Crunelle CL, Sabbe B, Neels H. Advances in detection of antipsychotics in biological matrices. Clin Chim Acta. 2015;441:11–22.  https://doi.org/10.1016/j.cca.2014.12.008.CrossRefGoogle Scholar
  25. 25.
    Khelfi A, Azzouz M, Abtroun R, Reggabi M, Alamir B. Determination of chlorpromazine, haloperidol, levomepromazine, olanzapine, risperidone, and sulpiride in human plasma by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Int J Anal Chem. 2018;2018:1–13.  https://doi.org/10.1155/2018/5807218.CrossRefGoogle Scholar
  26. 26.
    Nielsen MK, Johansen SS, Dalsgaard PW, Linnet K. Simultaneous screening and quantification of 52 common pharmaceuticals and drugs of abuse in hair using UPLC–TOF-MS. Forensic Sci Int. 2010;196:85–92.  https://doi.org/10.1016/j.forsciint.2009.12.027.CrossRefGoogle Scholar
  27. 27.
    Food and Drug Administration, Bioanalytical Method Validation Guidance for Industry, (2018)http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm (accessed 4 Feb 2019).
  28. 28.
    International Conference on Harmonisation (1996) Validation of analytical procedures: text and methodology Q2 (R1). Int Conf Harmon 11–12 . doi: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf accessed 4 Feb 2019).
  29. 29.
    Scientific Working Group for Forensic Toxicology (SWGTOX). Standard practices for method validation in forensic toxicology. J Anal Toxicol. 2013;37:452–74.CrossRefGoogle Scholar
  30. 30.
    Timmerman P, White S, Globig S, et al. EBF recommendation on the validation of bioanalytical methods for dried blood spots. Bioanalysis. 2011;3:1567–75.CrossRefGoogle Scholar
  31. 31.
    Abu-Rabie P, Denniff P, Spooner N, Brynjolffssen J, Galluzzo P, Sanders G. Method of applying internal standard to dried matrix spot samples for use in quantitative bioanalysis. Anal Chem. 2011;83:8779–86.  https://doi.org/10.1021/ac202321q.CrossRefGoogle Scholar
  32. 32.
    Bansal S, DeStefano A. Key elements of bioanalytical method validation for small molecules. AAPS J. 2007;9:E109–14.  https://doi.org/10.1208/aapsj0902017.CrossRefGoogle Scholar
  33. 33.
    World Anti-doping Agency, International standard for laboratories: identification criteria for qualitative assays incorporating column chromatography and mass spectrometry, (2010). https://www.wada-ama.org/sites/default/files/resources/files/WADA_TD2010IDCRv1.0_Identification%20Criteria%20for%20Qualitative%20Assays_May%2008%202010_EN.doc.pdf (accessed 6 Jan 2019).
  34. 34.
    Pujadas M, Pichini S, Civit E, Santamariña E, Perez K, de la Torre R. A simple and reliable procedure for the determination of psychoactive drugs in oral fluid by gas chromatography-mass spectrometry. J Pharm Biomed Anal. 2007;44:594–601.  https://doi.org/10.1016/j.jpba.2007.02.022.CrossRefGoogle Scholar
  35. 35.
    De Bièvre P, Günzler H. Validation in chemical measurement. 1st edition. Berlin: Springer-Verlag Berlin Heidelberg; 2005.Google Scholar
  36. 36.
    Fisher DS, van Schalkwyk GI, Seedat S, Curran SR, Flanagan RJ. Plasma, oral fluid, and whole-blood distribution of antipsychotics and metabolites in clinical samples. Ther Drug Monit. 2013;35:345–51.CrossRefGoogle Scholar
  37. 37.
    Langel K, Gunnar T, Ariniemi K, Rajamäki O, Lillsunde P. A validated method for the detection and quantitation of 50 drugs of abuse and medicinal drugs in oral fluid by gas chromatography–mass spectrometry. J Chromatogr B. 2011;879:859–70.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Débora Caramelo
    • 1
    • 2
  • Tiago Rosado
    • 1
    • 2
  • Victor Oliveira
    • 3
  • Jesus M. Rodilla
    • 4
    • 5
  • Pedro M. M. Rocha
    • 5
  • Mário Barroso
    • 6
  • Eugenia Gallardo
    • 1
    • 2
    Email author
  1. 1.Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior (CICS-UBI)CovilhãPortugal
  2. 2.Laboratório de Fármaco-Toxicologia – UBIMedicalUniversidade da Beira InteriorCovilhãPortugal
  3. 3.Centro Hospitalar Cova da Beira, E.P.E, Departamento de Psiquiatria e Saúde MentalCovilhãPortugal
  4. 4.Materiais Fibrosos e Tecnologias Ambientais – FibEnTech, Departamento de QuímicaUniversidade da Beira InteriorCovilhãPortugal
  5. 5.Departamento de QuímicaUniversidade da Beira InteriorCovilhãPortugal
  6. 6.Serviço de Química e Toxicologia ForensesInstituto de Medicina Legal e Ciências Forenses - Delegação do SulLisbonPortugal

Personalised recommendations