Detection of atomoxetine and its metabolites in the urine by thin-layer chromatography and mass spectrometry

Authors

DOI:

https://doi.org/10.14739/2409-2932.2022.1.252070

Keywords:

atomoxetine, hydroxyatomoxetine, dihydroxyatomoxetine, sample preparation, thin layer chromatography, mass spectrometry

Abstract

The aim of the study was the detection of atomoxetine and its biotransformation products in the urine under TLC screening conditions and identification of the metabolites using mass spectrometry method.

Materials and methods. The volunteer’s urine samples after taking a single therapeutic dose of atomoxetine (2 capsules of 60 mg each of Strattera®) were studied. Sample preparation included diluting acid hydrolysis followed by the native compound and metabolites extraction with chloroform from the saturated solution of ammonium sulfate at pH of 11–12. Thin-layer chromatography studies of the extracts were carried out in 18 mobile phases including those proposed by The International Association of Forensic Toxicologists for general drug screening, and those widely used in forensic toxicological studies. The color reactions were carried out using a range of chromogenic reagents. A Varian 1200 L mass spectrometer (Netherlands) equipped with a dual quadrupole mass analyzer was applied for analysis of the eluates from chromatograms. Identification was undertaken at the direct introduction of the sample into the ion chamber, electron-impact ionization (70 eV), and full ion scanning mode.

Results. The spot of the native drug on the chromatogram was identified by the Rf, value. Two atomoxetine biotransformation products were identified by the molecular weights that correspond to the molecular ion peaks in the mass spectra.

Conclusions. Atomoxetine and its biotransformation products were detected in the urine under TLC screening conditions and identified using mass spectrometry method. Chromatographic mobility of the native compound, hydroxyatomoxetine, and dihydroxyatomoxetine in the TLC screening systems as well as the results of their visualization using chromogenic reagents applied for toxicological drug screening in the systematic toxicological analysis have been determined.

Author Biographies

S. A. Karpushyna, National University of Pharmacy, Kharkiv, Ukraine

PhD, Associate Professor of the Department of Analytical Chemistry and Analytical Toxicology

S. V. Baiurka, National University of Pharmacy, Kharkiv, Ukraine

PhD, DSc, Professor of the Department of Analytical Chemistry and Analytical Toxicology

T. O. Tomarovska, National University of Pharmacy, Kharkiv, Ukraine

PhD, Associate Professor of the Department of Inorganic and Physical Chemistry

References

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

Baselt, C. R. (2020). Disposition of Toxic Drugs and Chemicals in Man, 12-th edition. Seal Beach, CA: Biomedical Publications.

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

Pilhatsch, M. K., Burghardt, R., Wandinger, K.-P., Bauer, M., & Adli, M. (2006). Augmentation with atomoxetine in treatment-resistant depression with psychotic features – a case report. Pharmacopsychiatry, 39(2), 79-80. https://doi.org/10.1055/s-2006-931547

Cesneková, D., Šnircová, E., Nosáľová, G., & Ondrejka, I. (2016). Is atomoxetine effective in some comorbid mental disorders in ADHD? European Pharmaceutical Journal, 63(1), 29-32. https://doi.org/10.1515/afpuc-2016-0003

Reed, V. A., Buitelaar, J. K., Anand, E., Day, K. A., Treuer, T., Upadhyaya, H. P., Coghill, D. R., Kryzhanovskaya, L. A., & 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. https://doi.org/10.1007/s40263-016-0349-0

Howes, С. F., & Sharp, C. (2018). Delusional infestation in the treatment of ADHD with atomoxetine. BMJ case repots, 2018, bcr2018226020. https://doi.org/10.1136/bcr-2018-226020

Başay, Ö., Basay, B. K., Öztürk, Ö., & Yüncü, Z. (2016). Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole. Clinical Psychopharmacology and Neuroscience, 14(2), 221-225. https://doi.org/10.9758/cpn.2016.14.2.221

Aronson, J. K. (2016). Atomoxetine. In Meyler's Side Effects of Drugs (16th ed., pp. 738-740.) Elsevier. https://www.sciencedirect.com/topics/medicine-and-dentistry/atomoxetine

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

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. https://doi.org/10.1111/j.1556-4029.2005.00021.x

Yu, G., Li, G.-F., Markowitz, J. S. (2016). Atomoxetine – A Review of its Pharmacokinetics and Pharmacogenomics Relative to Drug Disposition. Journal of Child and Adolescent Psychopharmacology, 26(4), 314-326. https://doi.org/10.1089/cap.2015.0137

Tomarovska, L. Yu., Baiurka, S. V., & Karpushina, S. A. (2017). Development of the methods for atomoxetine identification suitable for the chemical and toxicological analysis. Vìsnik farmacìï - News of Pharmacy, 2(90), 13-20. https://doi.org/10.24959/nphj.17.2154

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. https://doi.org/10.5958/0974-360X.2020.00760.X

Dinh, J. C., Pearce, R. E., Haandel, L. V., Gaedigk, A., & Leeder, J. S. (2016). Characterization of Atomoxetine Biotransformation and Implications for Development of PBPK Models for Dose Individualization in Children. Drug Metabolism & Disposition, 44(7), 1070-1079. https://doi.org/10.1124/dmd.116.069518

Sauer, J. M., Ponsler, G. D., Mattiuz, E. L., Long, A. J., Witcher, J. W., Thomasson, H. R., & Desante, K. A. (2003). Disposition and metabolic fate of atomoxetine hydrochloride: the role of CYP2D6 in human disposition and metabolism. Drug Metabolism & Disposition, 31(1), 98-107. https://doi.org/10.1124/dmd.31.1.98

Downloads

Published

2022-03-15

How to Cite

1.
Karpushyna SA, Baiurka SV, Tomarovska TO. Detection of atomoxetine and its metabolites in the urine by thin-layer chromatography and mass spectrometry. CIPM [Internet]. 2022Mar.15 [cited 2023Dec.8];15(1):25-30. Available from: http://pharmed.zsmu.edu.ua/article/view/252070

Issue

Vol. 15 No. 1 (2022)

Section

Original research

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.     Лицензия Creative Commons
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)