Skip to main content
Log in

Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography–tandem mass spectrometry

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

Abstract

A method using microextraction by packed sorbent (MEPS) and gas chromatography–tandem mass spectrometry (GC-MS/MS) is described for the determination of seven antipsychotic drugs in human plasma. The studied compounds were chlorpromazine (CPZ), haloperidol (HAL), cyamemazine, quetiapine, clozapine, olanzapine (OLZ), and levomepromazine; promazine, protriptyline, and deuterated CPZ were used as internal standards. The validation parameters included selectivity, linearity and limits of detection and quantitation, intra- and interday precision and trueness, recovery, and stability and were studied according to internationally accepted guidelines. The method was found to be linear between the lower limit of quantitation and 1000 ng/mL, except for OLZ and HAL (200 ng/mL), with determination coefficients higher than 0.99 for all analytes, and extraction efficiencies ranged from 62 to 92 %. Intra- and interday precision ranged from 0.24 to 10.67 %, while trueness was within a ±15 % interval from the nominal concentration for all analytes at all studied levels. MEPS has shown to be a rapid procedure for the determination of the selected antipsychotic drugs in human plasma, allowing reducing the handling time and the costs of analysis. Furthermore, GC-MS/MS has demonstrated to be a powerful tool for the simultaneous quantitation of the studied compounds, enabling obtaining adequate selectivity and sensitivity using a sample volume of as low as 0.25 mL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Rao LV, Snyder ML, Vallaro GM (2009) Rapid liquid chromatography/tandem mass spectrometer (LCMS) method for clozapine and its metabolite N-desmethyl clozapine (Norclozapine) in human serum. J Clin Lab Anal 23:394–398

    Article  CAS  Google Scholar 

  2. Saar E, Gerostamoulos D, Drummer OH, Beyer J (2010) Identification and quantification of 30 antipsychotics in blood using LC-MS/MS. J Mass Spectrom 45:915–925

    Article  CAS  Google Scholar 

  3. Zhang G, Terry AV Jr, Bartlett MG (2008) Bioanalytical methods for the determination of antipsychotic drugs. Biomed Chromatogr 22:671–687

    Article  CAS  Google Scholar 

  4. Zhang G, Terry AV Jr, Bartlett MG (2007) Simultaneous determination of five antipsychotic drugs in rat plasma by high performance liquid chromatography with ultraviolet detection. J Chromatogr B 856:20–28

    Article  CAS  Google Scholar 

  5. Mercolini L, Grillo M, Bartoletti C, Boncompagni G, Raggi MA (2007) Simultaneous analysis of classical neuroleptics, atypical antipsychotics and their metabolites in human plasma. Anal Bioanal Chem 388:235–243

    Article  CAS  Google Scholar 

  6. Mercolini L, Bugamelli F, Kenndler E, Boncompagni G, Franchini L, Raggi MA (2007) Simultaneous determination of the antipsychotic drugs levomepromazine and clozapine and their main metabolites in human plasma by a HPLC-UV method with solid-phase extraction. J Chromatogr B 846:273–280

    Article  CAS  Google Scholar 

  7. Cutroneo P, Beljean M, Luu RP, Siouffi AM (2006) Optimization of the separation of some psychotropic drugs and their respective metabolites by liquid chromatography. J Pharm Biomed Anal 41:333–340

    Article  CAS  Google Scholar 

  8. Bazhdanzadeh S, Talebpour Z, Adib N, Aboul-Enein HY (2011) A simple and reliable stir bar sorptive extraction-liquid chromatography procedure for the determination of chlorpromazine and trifluoperazine in human serum using experimental design methodology. J Sep Sci 34:90–97

    Article  CAS  Google Scholar 

  9. Kirchherr H, Kühn-Velten WN (2006) Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach. J Chromatogr B 843:100–113

    Article  CAS  Google Scholar 

  10. de la Torre C, Martínez MA, Almarza E (2005) Determination of several psychiatric drugs in whole blood using capillary gas–liquid chromatography with nitrogen phosphorus detection: comparison of two solid phase extraction procedures. Forensic Sci Int 155:193–204

    Article  Google Scholar 

  11. Vardakou I, Dona A, Pistos C, Alevisopoulos G, Athanaselis S, Maravelias C, Spiliopoulou C (2010) Validated GC/MS method for the simultaneous determination of clozapine and norclozapine in human plasma. Application in psychiatric patients under clozapine treatment. J Chromatogr B 878:2327–2332

    Article  CAS  Google Scholar 

  12. Saracino MA, Lazzara G, Prugnoli B, Raggi MA (2011) Rapid assays of clozapine and its metabolites in dried blood spots by liquid chromatography and microextraction by packed sorbent procedure. J Chromatogr A 1218:2153–2159

    Article  CAS  Google Scholar 

  13. Choong E, Rudaz S, Kottelat A, Guillarme D, Veuthey JL, Eap CB (2009) Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS. J Pharm Biomed Anal 50:1000–1008

    Article  CAS  Google Scholar 

  14. Hasselstrøm J (2011) Quantification of antidepressants and antipsychotics in human serum by precipitation and ultra high pressure liquid chromatography–tandem mass spectrometry. J Chromatogr B 879:123–128

    Article  Google Scholar 

  15. Tanaka E, Nakamura T, Terada M, Shinozuka T, Hashimoto C, Kurihara K, Honda K (2007) Simple and simultaneous determination for 12 phenothiazines in human serum by reversed-phase high-performance liquid chromatography. J Chromatogr B 854:116–120

    Article  CAS  Google Scholar 

  16. Rosland M, Szeto P, Procyshyn R, Barr AM, Wasan KM (2007) Determination of clozapine and its metabolite, norclozapine in various biological matrices using high-performance liquid chromatography. Drug Dev Ind Pharm 33:1158–1166

    Article  CAS  Google Scholar 

  17. Sachse J, Köller J, Härtter S, Hiemke C (2006) Automated analysis of quetiapine and other antipsychotic drugs in human blood by high performance-liquid chromatography with column-switching and spectrophotometric detection. J Chromatogr B 830:342–348

    Article  CAS  Google Scholar 

  18. Li J, Zhao F, Ju H (2006) Simultaneous determination of psychotropic drugs in human urine by capillary electrophoresis with electrochemiluminescence detection. Anal Chim Acta 575:57–61

    Article  CAS  Google Scholar 

  19. Lara FJ, García-Campaña AM, Alés-Barrero F, Bosque-Sendra JM (2005) Development and validation of a capillary electrophoresis method for the determination of phenothiazines in human urine in the low nanogram per milliliter concentration range using field-amplified sample injection. Electrophoresis 26:2418–2429

    Article  CAS  Google Scholar 

  20. Saar E, Beyer J, Gerostamoulos D, Drummer OH (2012) The analysis of antipsychotic drugs in human matrices using LC-MS(/MS). Drug Test Anal 4:376–394

    Article  CAS  Google Scholar 

  21. Zhang G, Terry AV Jr, Bartlett MG (2007) Sensitive liquid chromatography/tandem mass spectrometry method for the simultaneous determination of olanzapine, risperidone, 9-hydroxyrisperidone, clozapine, haloperidol and ziprasidone in rat brain tissue. J Chromatogr B 858:276–281

    Article  CAS  Google Scholar 

  22. Zhang G, Terry AV Jr, Bartlett MG (2007) Sensitive liquid chromatography/tandem mass spectrometry method for the determination of the lipophilic antipsychotic drug chlorpromazine in rat plasma and brain tissue. J Chromatogr B 854:68–76

    Article  CAS  Google Scholar 

  23. Niederländer HA, Koster EH, Hilhorst MJ, Metting HJ, Eilders M, Ooms B, de Jong GJ (2006) High throughput therapeutic drug monitoring of clozapine and metabolites in serum by on-line coupling of solid phase extraction with liquid chromatography–mass spectrometry. J Chromatogr B 834:98–107

    Article  Google Scholar 

  24. de Castro A, Fernandez MMR, Laloup M, Samyn N, Boeck G, Wood M, Maes V, López-Rivadulla M (2007) High-throughput on-line solid-phase extraction–liquid chromatography–tandem mass spectrometry method for the simultaneous analysis of 14 antidepressants and their metabolites in plasma. J Chromatogr A 1160:3–12

    Article  Google Scholar 

  25. Moreno IED, da Fonseca BM, Barroso M, Costa S, Queiroz JA, Gallardo E (2012) Determination of piperazine-type stimulants in human urine by means of microextraction in packed sorbent and high performance liquid chromatography–diode array detection. J Pharm Biomed Anal 61:93–99

    Article  CAS  Google Scholar 

  26. Miyaguchi H, Iwata Y, Kanamori T, Tsujikawa K, Kuwayama K, Inoue H (2009) Rapid identification and quantification of methamphetamine and amphetamine in hair by gas chromatography/mass spectrometry coupled with micropulverized extraction, aqueous acetylation and microextraction by packed sorbent. J Chromatogr A 1216:4063–4070

    Article  CAS  Google Scholar 

  27. Moreno IED, da Fonseca BM, Magalhães AR, Geraldes VS, Queiroz JA, Barroso M, Costa S, Gallardo E (2012) Rapid determination of piperazine-type stimulants in human urine by microextraction in packed sorbent after method optimization using a multivariate approach. J Chromatogr A 1222:116–120

    Article  CAS  Google Scholar 

  28. Abdel-Rehim M, Altun Z, Blomberg L (2004) Microextraction in packed syringe (MEPS) for liquid and gas chromatographic applications. Part II—determination of ropivacaine and its metabolites in human plasma samples using MEPS with liquid chromatography/tandem mass spectrometry. J Mass Spectrom 39:1488–1493

    Article  CAS  Google Scholar 

  29. Abdel-Rehim M (2010) Recent advances in microextraction by packed sorbent for bioanalysis. J Chromatogr A 1217:2569–2580

    Article  CAS  Google Scholar 

  30. Chaves A, Leandro F, Carris J, Queiroz ME (2010) Microextraction in packed sorbent for analysis of antidepressants in human plasma by liquid chromatography and spectrophotometric detection. J Chromatogr B 878:2123–2129

    Article  CAS  Google Scholar 

  31. Saracino MA, de Palma A, Boncompagni G, Raggi MA (2010) Analysis of risperidone and its metabolite in plasma and saliva by LC with coulometric detection and a novel MEPS procedure. Talanta 81:1547–1553

    Article  CAS  Google Scholar 

  32. International Conference on Harmonization (ICH), Validation of Analytical Procedures: Methodology ICH Q2 B. (2005). Available from http://www.ich.org/LOB/media/MEDIA417.pdf. Accessed 29 November 2011

  33. U.S. Department of Health and Human Services, Food and Drug Administration, Guidance for Industry: Bioanalytical Method Validation (2001). Available from http://www.fda.gov/downloads/Drugs/GuidanceCompilanceRegulatoryInformation/Guidances/ucm070107.pdf. Accessed 29 November 2011

  34. World Anti-doping Agency, International standard for laboratories: identification criteria for qualitative assays incorporating column chromatography and mass spectrometry (2010). Available from http://www.wadaama.org/Documents/World_AntiDoping_Program/WADP-IS-Laboratories/WADA_TD2010IDCRv1.0_IdentificationCriteriaforQualitativeAssays_May082010_EN.doc.pdf. Accessed 3 January 2012

  35. Barroso M, Costa S, Dias M, Vieira DN, Queiroz JA, López-Rivadulla M (2010) Analysis of phenylpiperazine-like stimulants in human hair as trimethylsilyl derivatives by gas chromatography–mass spectrometry. J Chromatogr A 1217:6274–6280

    Article  CAS  Google Scholar 

  36. Saar E, Gerostamoulos D, Drummer OH, Beyer J (2012) Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine. Forensic Sci Int 220:74–79

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the Protocol UBI/Santander-Totta in the form of two fellowships (Ivo Moreno and Beatriz da Fonseca), the program COMPETE and the Portuguese Foundation for Science and Technology (PEst-C/SAU/UI0709/2011).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Barroso.

Additional information

Published in the special paper collection Forensic Toxicology with guest editors Kazuhito Watanabe and Satoshi Chinaka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

da Fonseca, B.M., Moreno, I.E.D., Barroso, M. et al. Determination of seven selected antipsychotic drugs in human plasma using microextraction in packed sorbent and gas chromatography–tandem mass spectrometry. Anal Bioanal Chem 405, 3953–3963 (2013). https://doi.org/10.1007/s00216-012-6695-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-012-6695-y

Keywords

Navigation