DOI: https://doi.org/10.24959/cphj.20.1538

Laboratory toxicological diagnosis of fluoxetine poisonings

S. A. Karpushyna, S. V. Baiurka

Abstract


The results of laboratory diagnosis obtained during the toxicological study of human biological fluids for the presence of drugs are of key importance for determining the cause of the antidepressant poisoning.

Aim. To develop the bioanalytical method for determining the antidepressant fluoxetine in the blood and urine based on the high-performance liquid chromatography with a multiwave UV spectrophotometric detection, which is suitable for laboratory toxicological diagnosis of the antidepressant poisoning.

Materials and methods. The model blood and urine samples spiked with the antidepressant studied were analyzed. The extraction of the drug from biological fluids was performed with chloroform from the alkaline medium at pH of 8-9 in the presence of ammonium sulfate as a salting-out agent. The formed elements of blood were precipitated with 10 % trichloroacetic acid. The biological admixtures were removed by extraction with diethyl ether from the acidic medium and the TLC method. The chromatographic analysis was performed on a microcolumn chromatograph with a multiwave UV spectrophotometric detector on a reversed-phase C18 column.

Results. The retention time of fluoxetine in extracts from the blood and urine was 23.35 ± 0.03 min. The quantitative determination was performed at λmax 260 nm by the calibration curve of the dependence of the concentration on the peak area (μg/ml) y = (9.2∙10-5 ± 1∙10-6)x. Using the sample preparation method developed 58±4 % of fluoxetine was isolated from the blood, (72 ± 4) % of the drug from the urine.

Conclusions. The methods developed for the determination of fluoxetine in the blood and urine by the reversed-phase HPLC with a multiwave UVD after the liquid-liquid extraction at the stage of sample preparation have allowed to identify and determine the expected toxic and lethal concentrations of this antidepressant in biological fluids, and therefore, are suitable for the purpose of clinical and forensic toxicology.


Keywords


fluoxetine; biological fluids; extraction; high performance liquid chromatography

References


Fitzgerald, K. T, Bronstein, A. C. (2013). Selective serotonin reuptake inhibitor exposure. Topics in Companion Animal Medicine, 28 (2), 13-7. doi: https://doi.org/10.1053/j.tcam.2013.03.003

Wagle, B., Finn, M., Vanipenta, N. P. (2019). A Rare Overlap of Serotonin Syndrome and Status Epilepticus Confirmed on Electroencephalogram. Cureus Journal of Medical Science, 11 (5), 4667. doi: https://doi.org/10.7759/cureus.4667

Goulas, A., Raikos, N., Krokos, D., Mastrogianni, O., Orphanidis, A., Zisopoulos, K., Tsepa, A. (2018). Fatal intoxication with antidepressants: a case with many culprits. Forensic Science, Medicine and Pathology, 14 (2), 225-228. doi: https://doi.org/10.1007/s12024-018-9960-3

Groot, J. A. N., Bokum, L. T., Oever, H. L. A. van den. (2018). Late presentation of Torsades de Pointes related to fluoxetine following a multiple drug overdose. Journal of Intensive Care, 10 (6), 59. doi: https://doi.org/10.1186/s40560-018-0329-1

Proença, P., Franco, J. M., Mustra, C., Monteiro, C., Costa, J., Corte-Real, F., Vieira, D. N. (2013). UPLC-MS/MS determination in blood of a mixed-drug fatal intoxication: a case report. Forensic Science International, 227 (1-3), 85-89. doi: https://doi.org/10.1016/j.forsciint.2012.10.038

Wu, M.-L., Deng, J.-F. (2011). Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose. Chang Gung Medical Journal, 34 (6), 644-649. Available at: http://cgmj.cgu.edu.tw/3406/340611.pdf

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: Pharmaceutical Press, 2736.

Baselt, C. R. (2011). Disposition of Toxic Drugs and Chemicals in Man. (9-th ed.). Seal Beach, California: Biomedical Publications, 1900.

Kazartsev, I. А., Fedoseeva, L. М. (2011). Farmatsyia, 7, 17-18.

Unceta, N., Ugarte, A., Sánchez, A. (2010). Development of a stir bar sorptive extraction based HPLC-FLD method for the quantification of serotonin reuptake inhibitors in plasma, urine and brain tissue samples. Journal of Pharmaceutical and Biomedical Analysis, 51 (1), 178-185. doi: https://doi.org/10.1016/j.jpba.2009.07.015

Freitas, D. F., Porto, C. E., Vieira, E. P., Siqueira, M. E. (2010). Three-phase, liquid-phase microextraction combined with high performance liquid chromatography-fluorescence detection for the simultaneous determination of fluoxetine and norfluoxetine in human plasma. Journal of Pharmaceutical and Biomedical Analysis, 51 (1), 170-177 doi: https://doi.org/10.1016/j.jpba.2009.07.017

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: https://doi.org/10.1097/FTD.0b013e31823bf0fd

Poklis, J. L., Wolf, C. E., Goldstein, A. G. (2012). Detection and Quantification of Tricyclic Antidepressants and Other Psychoactive Drugs in Urine by HPLC/MS/MS for Pain Management Compliance Testing. Journal of Clinical Laboratory Analysis, 26 (4), 286-294. doi: https://doi.org/10.1002/jcla.21519

Tomarovska, L. Yu., Baiurka, S. V., Karpushina, S. A. (2020). Study of Solvent extraction of Atomoxetine from Aqueous solutions and Biological fluids. Research Journal of Pharmacy and Technology, 13 (9), 4303-4309. doi: https://doi.org/10.5958/0974-360X.2020.00760.X


GOST Style Citations


1.   Fitzgerald K. T., Bronstein A. C. Selective serotonin reuptake inhibitor exposure. Top Companion Anim. Med. 2013. Vol. 28, Iss. 2. P. 13–7. DOI: https://doi.org/10.1053/j.tcam.2013.03.003

 

2.   Wagle B., Finn M., Vanipenta N. P. A rare overlap of serotonin syndrome and status epilepticus confirmed on electroencephalogram. Cureus. 2019. Vol. 11, Iss. 5. P. 4667. DOI: https://doi.org/10.7759/cureus.4667

 

3.   Fatal intoxication with antidepressants: a case with many culprits / А. Goulas et al. Forensic Sci. Med. Pathol. 2018. Vol. 14, Iss. 2. P. 225–228. DOI: https://doi.org/10.1007/s12024-018-9960-3

 

4.   Groot J. A. N., Bokum L. T., Oever H. L. Late presentation of torsades de pointes related to fluoxetine following a multiple drug overdose. Journal of Intensive Care. 2018. Vol. 10, Iss. 6. P. 59. DOI: https://doi.org/10.1186/s40560-018-0329-1

 

5.   UPLC-MS/MS determination in blood of a mixed-drug fatal intoxication : a case report / Р. Proenca et al. Forensic Sci. Int. 2013. Vol. 227, Iss. 1–3. P. 85–89. DOI: https://doi.org/10.1016/j.forsciint.2012.10.038

 

6.   Wu M.-L., Deng J.-F. Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose. Chang. Gung. Med J. 2011. Vol. 34, Iss. 6. P. 644–649. URL: http://cgmj.cgu.edu.tw/3406/340611.pdf

 

7.   Moffat A. C., Osselton M. D., Widdop B. Clarke’s analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material. 4-th ed. London, Chicago : Pharmaceutical Press, 2011. 2736 p.

 

8.   Baselt C. R. Disposition of toxic drugs and chemicals in man. 9-th ed. Seal Beach, California : Biomedical Publications, 2011. 1900 p.

 

9.   Казарцев И. А., Федосеева Л. М. Определение кетамина и флуоксетина в сочетании с лекарственными препаратами. Фармация. 2011. № 7. С. 17–18.

 

10. Unceta N., Ugarte A., Sánchez A. Development of a stir bar sorptive extraction based HPLC-FLD method for the quantification of serotonin reuptake inhibitors in plasma, urine and brain tissue samples. J. Pharm. Biomed. Anal. 2010. Vol. 51, Iss. 1. P. 178–185. DOI: https://doi.org/10.1016/j.jpba.2009.07.015

 

11. Three-phase, liquid-phase microextraction combined with high performance liquid chromatography-fluorescence detection for the simultaneous determination of fluoxetine and norfluoxetine in human plasma / D. F. Freitas at al. J. Pharm. Biomed. Anal. 2010. Vol. 51, Iss. 1. P. 170-177. DOI: https://doi.org/10.1016/j.jpba.2009.07.017

 

12. Fernаndez M. R., Wille S. M., Samyn N. Quantitative method validation for the analysis of 27 antidepressants and metabolites in plasma with ultraperformance liquid chromatography-tandem mass spectrometry. Ther. Drug Monit. 2012. Vol. 34, Iss. 1. P. 11–24. DOI: https://doi.org/10.1097/FTD.0b013e31823bf0fd

 

13. Poklis J. L., Wolf C. E., Goldstein A. G. Detection and quantification of tricyclic antidepressants and other psychoactive drugs in urine by HPLC/MS/MS for pain management compliance testing. J. Clin. Lab. Anal. 2012. Vol. 26, Iss. 4. P. 286–294. DOI: https://doi.org/10.1002/jcla.21519

 

14. Tomarovska L. Y., Baiurka S. V., Karpushina S. A. Study of solvent extraction of atomoxetine from aqueous solutions and biological fluids. Research J. Pharm. and Tech. 2020. Vol. 13, Iss. 9. P. 4303–4309. DOI: https://doi.org/10.5958/0974-360X.2020.00760.X





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Abbreviated key title: Clin. pharm.

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