Salt-assisted liquid–liquid microextraction for determination of haloperidol in human plasma by LC-MS/MS


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DOI:

https://doi.org/10.62063/ecb-16

Keywords:

haloperidol, LC-MS/MS, SALLME, TDM

Abstract

Haloperidol is an antipsychotic used in the treatment of schizophrenia. Compared to other antipsychotics, it is widely used in developing countries due to its affordable price. Haloperidol has a narrow therapeutic range and variable pharmacokinetics; therefore, therapeutic drug monitoring (TDM) is recommended. For this reason, in this study, an easily applicable, fast, selective, accurate, reliable, and economical LC-MS/MS method was developed for the determination of haloperidol in human plasma for use in TDM and also method was validated according to European Medicines Agency (EMA) Bioanalytical method validation guidelines. In the developed method, analyte and internal standard were extracted from plasma by salt-assisted liquid-liquid microextraction (SALLME) technique and after that injected to the LC system. The limit of quantification of haloperidol was determined as 1 ng/ml. The calibration curve was validated between 1-15 ng/ml, with correlation coefficients >0.99. In addition, the developed method was used to determine drug concentration levels in the plasma of real patients.

References

Agency, E.M., 2011. Guideline on bioanalytical method validation. EMEA/CHMP/EWP/192217/2009.

Ates, H. C., Roberts, J. A., Lipman, J., Cass, A. E. G., Urban, G. A., & Dincer, C. (2020). On-site therapeutic drug monitoring. Trends in biotechnology, 38(11), 1262-1277. https://doi.org/10.1016/j.tibtech.2020.03.001

Brockmöller, J., Kirchheiner, J., Schmider, J., Walter, S., Sachse, C., Müller-Oerlinghausen, B., & Roots, I. (2002). The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment. Clinical pharmacology and therapeutics, 72(4), 438-452. https://doi.org/10.1067/mcp.2002.127494

Cao, Y., Zhao, F., Chen, J., Huang, T., Zeng, J., Wang, L., Sun, X., Miao, Y., Wang, S., & Chen, C. (2020). A simple and rapid LC-MS/MS method for the simultaneous determination of eight antipsychotics in human serum, and its application to therapeutic drug monitoring. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1147, 122129. https://doi.org/10.1016/j.jchromb.2020.122129

Degreef, M., Berry, E. M., Maudens, K. E. K., & van Nuijs, A. L. N. (2021). Multi-analyte LC-MS/MS quantification of 38 antipsychotics and metabolites in plasma: Method validation & application to routine analyses. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 1179, 122867. https://doi.org/10.1016/j.jchromb.2021.122867

Domingues, D. S., Pinto, M. A., de Souza, I. D., Hallak, J. E., Crippa, J. A., & Queiroz, M. E. (2016). Determination of Drugs in Plasma Samples by High-Performance Liquid Chromatography-Tandem Mass Spectrometry for Therapeutic Drug Monitoring of Schizophrenic Patients. Journal of analytical toxicology, 40(1), 28-36. https://doi.org/10.1093/jat/bkv107

Eliasson, E., Lindh, J. D., Malmström, R. E., Beck, O., & Dahl, M. L. (2013). Therapeutic drug monitoring for tomorrow. European journal of clinical pharmacology, 69 Suppl 1, 25-32. https://doi.org/10.1007/s00228-013-1504-x

Gassó, P., Papagianni, K., Mas, S., de Bobadilla, R. F., Arnaiz, J. A., Bernardo, M., & Lafuente, A. (2013). Relationship between CYP2D6 genotype and haloperidol pharmacokinetics and extrapyramidal symptoms in healthy volunteers. Pharmacogenomics, 14(13), 1551-1563. https://doi.org/10.2217/pgs.13.150

Gerace, E., Salomone, A., Pellegrino, S., & Vincenti, M. (2012). Evidence of Haldol (haloperidol) long-term intoxication. Forensic science international, 215(1-3), 121-123. https://doi.org/10.1016/j.forsciint.2011.01.038

Gradinaru, J., Vullioud, A., Eap, C. B., & Ansermot, N. (2014). Quantification of typical antipsychotics in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry for therapeutic drug monitoring. Journal of pharmaceutical and biomedical analysis, 88, 36-44. https://doi.org/10.1016/j.jpba.2013.07.041

Grubor, M., Zivkovic, M., Sagud, M., Nikolac Perkovic, M., Mihaljevic-Peles, A., Pivac, N., Muck-Seler, D., & Svob Strac, D. (2020). HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia. International journal of molecular sciences, 21(7), 2345. https://doi.org/10.3390/ijms21072345

Gupta, M., Jain, A., & Verma, K. K. (2009). Salt-assisted liquid-liquid microextraction with water-miscible organic solvents for the determination of carbonyl compounds by high-performance liquid chromatography. Talanta, 80(2), 526-531. https://doi.org/10.1016/j.talanta.2009.07.021

Hempenius, J., Steenvoorden, R. J., Lagerwerf, F. M., Wieling, J., & Jonkman, J. H. (1999). 'High throughput' solid-phase extraction technology and turbo ionspray LC-MS-MS applied to the determination of haloperidol in human plasma. Journal of pharmaceutical and biomedical analysis, 20(6), 889-898. https://doi.org/10.1016/s0731-7085(99)00107-7

Hiemke, C., Bergemann, N., Clement, H. W., Conca, A., Deckert, J., Domschke, K., Eckermann, G., Egberts, K., Gerlach, M., Greiner, C., Gründer, G., Haen, E., Havemann-Reinecke, U., Hefner, G., Helmer, R., Janssen, G., Jaquenoud, E., Laux, G., Messer, T., Mössner, R., … Baumann, P. (2018). Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry, 51(1-02), e1. https://doi.org/10.1055/s-0037-1600991

Juenke, J. M., Brown, P. I., Urry, F. M., Johnson-Davis, K. L., & McMillin, G. A. (2013). Simultaneous UPLC-MS/MS assay for the detection of the traditional antipsychotics haloperidol, fluphenazine, perphenazine, and thiothixene in serum and plasma. Clinica chimica acta; international journal of clinical chemistry, 423, 32-34. https://doi.org/10.1016/j.cca.2013.04.014

Khelfi, A., Azzouz, M., Abtroun, R., Reggabi, M., & Alamir, B. (2018). Determination of Chlorpromazine, Haloperidol, Levomepromazine, Olanzapine, Risperidone, and Sulpiride in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS). International journal of analytical chemistry, 2018, 5807218. https://doi.org/10.1155/2018/5807218

Kudo, S., & Ishizaki, T. (1999). Pharmacokinetics of haloperidol: an update. Clinical pharmacokinetics, 37(6), 435-456. https://doi.org/10.2165/00003088-199937060-00001

Lally, J., & MacCabe, J. H. (2015). Antipsychotic medication in schizophrenia: a review. British medical bulletin, 114(1), 169-179. https://doi.org/10.1093/bmb/ldv017

Lee, Y., Wang, P. K., Lai, H. Y., Yang, Y. L., Chu, C. C., & Wang, J. J. (2007). Haloperidol is as effective as ondansetron for preventing postoperative nausea and vomiting. Canadian journal of anaesthesia = Journal canadien d'anesthesie, 54(5), 349–354. https://doi.org/10.1007/BF03022656

Leucht, C., Kitzmantel, M., Chua, L., Kane, J., & Leucht, S. (2008). Haloperidol versus chlorpromazine for schizophrenia. The Cochrane database of systematic reviews, (1), CD004278. https://doi.org/10.1002/14651858.CD004278.pub2

Montenarh, D., Hopf, M., Maurer, H. H., Schmidt, P., & Ewald, A. H. (2016). Development and validation of a multi-analyte LC-MS/MS approach for quantification of neuroleptics in whole blood, plasma, and serum. Drug testing and analysis, 8(10), 1080-1089. https://doi.org/10.1002/dta.1923

Remane, D., Meyer, M. R., Wissenbach, D. K., & Maurer, H. H. (2011). Ultra high performance liquid chromatographic-tandem mass spectrometric multi-analyte procedure for target screening and quantification in human blood plasma: validation and application for 31 neuroleptics, 28 benzodiazepines, and Z-drugs. Analytical and bioanalytical chemistry, 401(4), 1341-1352. https://doi.org/10.1007/s00216-011-5187-9

Shin, J. G., Kane, K., & Flockhart, D. A. (2001). Potent inhibition of CYP2D6 by haloperidol metabolites: stereoselective inhibition by reduced haloperidol. British journal of clinical pharmacology, 51(1), 45-52. https://doi.org/10.1046/j.1365-2125.2001.01313.x

Tuzimski, T., & Petruczynik, A. (2020). Review of Chromatographic Methods Coupled with Modern Detection Techniques Applied in the Therapeutic Drugs Monitoring (TDM). Molecules (Basel, Switzerland), 25(17), 4026. https://doi.org/10.3390/molecules25174026

Tyler, M. W., Zaldivar-Diez, J., & Haggarty, S. J. (2017). Classics in Chemical Neuroscience: Haloperidol. ACS chemical neuroscience, 8(3), 444–453. https://doi.org/10.1021/acschemneuro.7b00018

Vella-Brincat, J., & Macleod, A. D. (2004). Haloperidol in palliative care. Palliative medicine, 18(3), 195–201. https://doi.org/10.1191/0269216304pm881oa

Wang, E. H., Mabasa, V. H., Loh, G. W., & Ensom, M. H. (2012). Haloperidol dosing strategies in the treatment of delirium in the critically ill. Neurocritical care, 16(1), 170–183. https://doi.org/10.1007/s12028-011-9643-3

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Published

2024-01-02

How to Cite

Al, S., Kul, A., & Sagirli, O. (2024). Salt-assisted liquid–liquid microextraction for determination of haloperidol in human plasma by LC-MS/MS. The European Chemistry and Biotechnology Journal, (1), 39–46. https://doi.org/10.62063/ecb-16

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Research Articles