Dеvelopment of the analytical diagnostics of atomoxetine poisonings

Authors

  • S. A. Karpushyna National University of Pharmacy, Ukraine https://orcid.org/0000-0001-8834-4286
  • S. V. Baiurka National University of Pharmacy, Ukraine
  • L. Yu. Tomarovska National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/cphj.19.1482

Keywords:

atomoxetine, general isolation methods, thin-layer chromatography, UV-spectrophotometry

Abstract

Atomoxetine is one of the main drugs used for the treatment of attention-deficit/hyperactivity disorder. The drug has repeatedly been the cause of fatal poisonings. Data on atomoxetine determination in the biological material are missing in the literature.

Aim. To determine the recovery of the methods generally accepted in chemicotoxicological analysis for drug isolation from the biological material with regard to atomoxetine.

Materials and methods. The study was performed with the model animal liver samples containing the drug under research. The detection and quantitative determination of the drug in the extracts was performed using thin-layer chromatography, color reactions and UV spectrophotometry.

Results. The recovery of the drug isolation was of 31.6 ± 3.0 % according to A. A Vasylieva’s method, 25.6±2.9 % according to Stas-Otto’s method, and 26.8 ± 2.8 % according to V. Ph. Kramarenko’s method. The limits of detection (LOD) and quantitative determination (LOQ) of the UV-spectrophotometric method for determination of atomoxetine in the biological material depending on the sample preparation method were determined. The LOD and LOQ values were 5.3 and 16.2 μg/ml (using A. A. Vasylieva’s method) and 2.3 and 7.1 μg/ml (using V. Ph. Kramarenko’s method), respectively. These values exceeded the corresponding values obtained for the standard solutions of atomoxetine, they were of 1.8 and 5.6 μg/ml, respectively. The LOD and LOQ values corresponding to isolation by Stas-Otto’s method were of 1.7 and 5.3 μg/ml, respectively.

Сonclusions. Isolation according to Stas-Otto’s method has provided the highest selectivity of the UV-spectrophotometric method for atomoxetine determination in the biological material with regard to the matrix components.

Author Biographies

S. A. Karpushyna, National University of Pharmacy

доцент кафедри лікарської і аналітичної токсикології

S. V. Baiurka, National University of Pharmacy

завідувач  кафедри лікарської і аналітичної токсикології

L. Yu. Tomarovska, National University of Pharmacy

аспірант

References

Childress, A. C. (2015). A critical appraisal of atomoxetine in the management of ADHD. Therapeutics and Clinical Risk Management, 12, 27 – 39. doi: 10.2147/TCRM.S59270. eCollection 2016

Reed, V. A., Buitelaar, J. K., Anand, E., Day, K. A., Treuer, T., Upadhyaya, H. P., Savill, N. C. (2016). The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research. CNS drugs, 30 (7), 603 – 628. doi: 10.1007/s40263-016-0349-0

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

Paxton, G. A., Cranswick, N. E. (2008). Acute suicidality after commencing atomoxetine. Journal of Paediatrics and Child Health, 44 (10), 596 – 598. doi: 10.1111/j.1440-1754.2008.01389.x

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

Garside, D., Ropero-Miller, J. D., Riemer, E. C. (2006). Postmortem tissue distribution of atomoxetine following fatal and nonfatal doses – three case reports. Journal of Forensic Sciences, 51 (1), 179 – 182. doi: 10.1111/j.1556–4029.2005.00021.x

Patel, C., Patel, M., Rani, S., Nivsarkar, M., Padh, H. (2007). A new high performance liquid chromatographic method for quantification of atomoxetine in human plasma and its application for pharmacokinetic study. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 850 (1 – 2), 356 – 360. doi: 10.1016/j.jchromb.2006.12.011

Guo, W., Li, W., Guo, G., Zhang, J., Zhou, B., Zhai, Y., Wang, C. (2007). Determination of atomoxetine in human plasma by a high performance liquid chromatographic method with ultraviolet detection using liquid-liquid extraction. Journal of Chromatography B, 854 (1), 128 – 134. doi: 10.1016/j.jchromb.2007.04.007

Shang, D. W., Guo, W., Zhou, F. C., Wang, X. P., Li, A. N., Zhang, L., Wang, C. Y. (2013). Relative bioequivalence evaluation of two oral atomoxetine hydrochloride capsules: a single dose, randomized, open-label, 2-period crossover study in healthy Chinese volunteers under fasting conditions. Drug Research, 63 (11), 564 – 567. doi: 10.1055/s-0033-1349070

Zhu, H. J., Wang, J. S., Donovan, J. L., De Vane, C. L., Gibson, B. B., Markowitz, J. S. (2007). Sensitive quantification of atomoxetine in human plasma by HPLC with fluorescence detection using 4-(4,5-diphenyl-1H-imidazole-2-yl) benzoyl chloride derivatization. Journal of Chromatography B. Analytical Technologies in the Biomedical and Life Sciences. 846 (1 2), 351–354.

Mullen, J. H., Shugert, R. L., Ponsler, G. D., Li, Q., Sundaram, B., Coales, H. L., Sauer, J. M. (2005). Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS). Journal of Pharmaceutical and Biomedical Analysis, 38 (4), 720 – 733. doi: 10.1016/j.jpba.2005.02.007

Appel, D. I., Brinda, B., Markowitz, J. S., Newcorn, J. H., Zhu, H. J. (2012). A liquid chromatography/tandem mass spectrometry assay for the analysis of atomoxetine in human plasma and in vitro cellular samples. Biomedical Chromatography, 26 (11), 1364 – 1370. doi: 10.1002/bmc.2706

Zeng, H. J., Yang, R., Zhang, Y., Li, J. J., Qu, L. B. (2015). Capillary electrophoresis coupled with electrochemiluminescence for determination of atomoxetine hydrochloride and the study on its interactions with three proteins. Luminescence, 30 (2), 124 – 130. doi: 10.1002/bio.2700

Баюрка, С. В., Бондар, В. С., Мерзлікін, С. І., Карпушина, С. А., Погосян, О. Г., Полуян, С. М., Степаненко, В. І., Шовкова, З. В., Нетьосова, К. Ю., Москаленко, В. Ю., Ковальов, В. М. (2017). Аналітична токсикологія: навч. посіб. для студентів вищ. навч. закл. Х. : НФаУ : Золоті сторінки, 384.

Крамаренко, В. П. (1995). Токсикологічна хімія. К. : Вища шк., 423.

Tomarovska, L. Yu., Baiurka, S. V., Karpushyna, S. A. (2017). Development of the methods for atomoxetine identification suitable for the chemical and toxicological analysis. Visnik Farmacії, 2 (90), 13 – 20. doi: 10.24959/nphj.17.2154

Tomarovska, L. Yu., Baiurka, S. V., Karpushyna, S. A. (2017). Development of the UV-spectrophotometric and extraction-spectrophotometric methods of the atomoxetine quantitative determination suitable for the chemical and toxicological analysis. Visnik Farmacії, 4 (92), 15 – 19. doi: 10.24959/nphj.17.2191

Baiurka, S. V., Karpushyna, S. A., Tomarovska, L. Yu. (2018). Determination of the optimum conditions for solvent extraction of atomoxetine from biological fluids. New trends in the scientific world: Proceedings of XХVІ International scientific conference (Morrisville, Septenber 8, 2018). Morrisville : Lulu Press, 102 – 103.

Derzhavna Farmakopeia Ukrainy, 1-st ed. (2008). Kh. : “Naukovo-ekspertnyi farmakopeinyi tsentr”, 620.

ICH Harmonised Tripartite Guideline. Validation of Analytical Procedures: Text and Methodology Q2(R1). Current Step 4 version. (2005). [Electronic resource], 13. Available at: http://www.ich.org/fileadmin/Public_Web-_Site/ICH_Products/Guidelines/-Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf.

Published

2019-03-04

Issue

Section

Pre-clinical studies of new drugs