Development of conditions for isolation of antidepressant paroxetine from biological fluids

Authors

DOI:

https://doi.org/10.24959/nphj.24.133

Keywords:

paroxetine, biological fluids, extraction, UV spectrophotometry

Abstract

Aim. To develop optimized conditions for isolating the new antidepressant paroxetine from model blood and urine samples by the liquid extraction followed by the determination of the analyte using the UV spectrophotometric method.

Materials and methods. The studies were performed with model samples of the donor blood and urine spiked with paroxetine. In the sample preparation of blood, the form elements were previously precipitated by 10 % solution of trichloroacetic acid. Endogenous impurities were removed by the extraction purification with chloroform from an acidic medium at pH 1, and paroxetine was extracted from the biological fluids under study with ethyl acetate at pH 10. The organic extracts obtained were further purified using the TLC method. After that, the determination of paroxetine in the eluates obtained from chromatograms was performed using the UV spectrophotometric method.

Results and discussion. The Rf value of paroxetine in the mobile phase of ethyl acetate-methanol-25 % ammonium hydroxide solution (85:15:10) was 0.42 ± 0.02. The UV spectra of eluates from chromatograms had absorption maxima at wavelengths of 265 ± 2, 272 ± 2 and 293 ± 2 nm and matched with the UV spectrum of a standard solution of paroxetine in 0.1 M solution of hydrochloric acid. The quantitative determination was performed at λmax293 nm according to the equation of the calibration curve y=0.0094x–0.02. The methods developed allowed to isolate 70.0 ± 4.0 % of paroxetine from the urine, 26.0 ± 3.0 % from the blood plasma and additionally 5.4 ± 0.6 % of the antidepressant studied from the blood cell sediment after its preliminary separation from the blood plasma.

Conclusions. The optimized conditions for sample preparation of model blood and urine samples by the liquid extraction method in relation to paroxetine have been determined. The results obtained are of applied practical significance for creating an algorithm in the toxicological study of biological fluids for the presence of this antidepressant in fatal drug intoxications.

Author Biographies

S. A. Karpushyna, Uman National University of Horticulture, Ukraine

Candidate of Chemistry (Ph.D.), associate professor of the Department of Biology

S. V. Baiurka, National University of Pharmacy of the Ministry of Health of Ukraine, Kharkiv

Doctor of Pharmacy (Dr. habil.), professor of the Department of Medicinal Chemistry

I. Y. Halkevych, Danylo Halytsky Lviv National Medical University, Ukraine

Candidate of Pharmacy (Ph.D.), associate professor, head of the Department of Toxicological and Analytical Chemistry

S. I. Ihlitska, Danylo Halytsky Lviv National Medical University, Ukraine

Candidate of Pharmacy (Ph.D.), acting associate professor of the Department of Toxicological and Analytical Chemistry

O. O. Altukhov, Kharkiv Scientific Research Forensic Center of the Ministry of Internal Affairs of Ukraine

Associate professor, forensic expert of the Department of Materials, Substances  and Products

I. E. Bylov, Kharkiv Scientific Research Forensic Center of the Ministry of Internal Affairs of Ukraine

PhD, Candidate of Pharmacy (Ph.D.), associate professor of the Department of General Chemistry

References

Guaiana, G., Meader, N., Barbui, C., Davies, S. J., Furukawa, T. A., Imai, H. et al. (2023). Pharmacological treatments in panic disorder in adults: a network meta-analysis. Cochrane Database of Systematic Reviews, 11 (11), CD012729. doi: 10.1002/14651858.CD012729.pub3.

Hudd, T. R., Blake, C. S., Rimola-Dejesus, Y., Nguyen, T.-T., Zaiken, K. A. Case Report of Serotonin. (2020). Syndrome in a Patient on Selective Serotonin Reuptake Inhibitor (SSRI) Monotherapy. Journal of Pharmacy Practice, 33 (2), 206-212. doi:10.1177/0897190019841742.

Moffat, A. C., Osselton, M. D., Widdop, B. (2011). Clarke’s analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material. (4-th ed.). London, Chicago.

Baselt C. R. (2011). Disposition of Toxic Drugs and Chemicals in Man. Seal Beach, California.

Fernández, M. R., Wille, S. M., Samyn, N. (2012). Quantitative method validation for the analysis of 27 antidepressants and metabolites in plasma with ultraperformance liquid chromatography-tandem mass spectrometry. Therapeutic Drug Monitoring, 34 (1), 11-24. doi: 10.1097/FTD.0b013e31823bf0fd.

Eibak, L. E., Gjelstad, A., Rasmussen, K. E., Pedersen-Bjergaard, S. (2012). Exhaustive electromembrane extraction of some basic drugs from human plasma followed by liquid chromatography-mass spectrometry Journal of Pharmaceutical and Biomedical Analysis, 57, 33-38. doi: 10.1016/j.jpba.2011.08.026.

Cai, P., Xiong, X., Li, D., Zhou, Y., Xiong, C. (2020). Magnetic solid-phase extraction coupled with UHPLC-MS/MS for four antidepressants and one metabolite in clinical plasma and urine samples. Bioanalysis, 12 (1), 35-52. doi: 10.4155/bio-2019-0171.

Ma, W., Gao, X., Guo, H., Chen, W. (2021). Determination of 13 antidepressants in blood by UPLC-MS/MS with supported liquid extraction pretreatment. Journal of Chromatography B, Analytical Technologies in the Biomedical Life Sciences, 1171, 122608. doi: 10.1016/j.jchromb.2021.122608.

Amundsen, I., Oiestad, A. M., Ekeberg, D., Kristoffersen, L. (2013). Quantitative determination of fifteen basic pharmaceuticals in ante- and post-mortem whole blood by high pH mobile phase reversed phase ultra high performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography B, Analytical Technologies in the Biomedical Life Sciences, 927 (1), 112-123. doi: 10.1016/j.jchromb.2012.12.039.

Snamina, M., Wietecha-Posłuszny, R., Zawadzki, M. (2019). Postmortem analysis of human bone marrow aspirate – Quantitative determination of SSRI and SNRI drugs. Talanta, 204, 607-612. doi: 10.1016/j.talanta.2019.06.054.

Papoutsis, I., Khraiwesh, A., Nikolaou, P., Pistos, C., Spiliopoulou, C., Athanaselis, S. (2012). A fully validated method for the simultaneous determination of 11 antidepressant drugs in whole blood by gas chromatography–mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 70, 557-562. doi: 10.1016/j.jpba.2012.05.007.

Cabarcos-Fernández, P., Tabernero-Duque, M. J., Álvarez-Freire, I., Bermejo-Barrera, A. M. (2021). Determination of Seven Antidepressants in Pericardial Fluid by Means of Dispersive Liquid-Liquid Microextraction (DLLME) and Gas Chromatography-Mass Spectrometry (GC/MS). Journal of Analytical Toxicology, 46 (1), 146-56. doi: 10.1093/jat/bkab003.

Das, R., Agrawal, Y. K. (2013). Simultaneous Monitoring of Selective Serotonin Reuptake Inhibitors in Human Urine, Plasma and Oral Fluid by Reverse-Phase High Performance Liquid Chromatography. Journal of Chromatographic Science, 51 (2), 146-154. doi: 10.1093/chromsci/bms119.

Jickells, S., Negrusz, A. (Eds.). (2008). Clarke’s Analytical Forensic Toxicology. London.

American Board of Forensic Toxicology “Forensic Toxicology Laboratory Accreditation Checklist”. (2023, July). Available at: https://www.abft.org/wp-content/uploads/2023/04/ABFT_LAP-Checklist_2023-v.Jan-31.pdf.

Published

2024-03-20

Issue

Section

Articles