Development of the methods for atomoxetine identification suitable for the chemical and toxicological analysis

Authors

  • L. Yu. Tomarovska National University of Pharmacy, Ukraine
  • S. V. Baiurka National University of Pharmacy, Ukraine
  • S. A. Karpushyna National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/nphj.17.2154

Keywords:

atomoxetine, TLC-screening, UV-spectrum

Abstract

The cases of acute and lethal poisonings by atomoxetine, an antidepressant, have been registered. Therefore, development of the available and reliable methods for its chemical and toxicological analysis is the topical issue.
Aim. To develop the conditions for atomoxetine detection in the presence of a number of its pharmacological and structural analogs when performing the general TLC-screening and identification of the antidepressant by UV spectrophotometry.
Materials and methods. Chromatographic mobility of antidepressants in thin sorbent layers was studied in 11 mobile phases, including those recommended by TIAFT, using five types of chromatographic plates. A number of chromogenic reagents was used for visualization. The UV-spectrum of atomoxetine was studied in 0.1 Mol • L-1 solution of hydrochloric acid.
Results and discussion. Chromatographic systems with the low correlation of Rf values for atomoxetine that make them suitable for the general TLC-screening have been found. The UV spectrum of atomoxetine in the acid solution had light absorption maxima at wavelengths of 270 (ε = 1300; A11 = 45) and 277 nm.
Conclusions. A combined use of three mobile phases: methanol – 25 % ammonia solution (100 : 1.5), cyclohexane – toluene – diethylamine (75 : 15 : 10), and toluene – acetone – 25 % ammonia solution (45 : 45 : 7.5 : 2.5) provides a reliable atomoxetine detection in the presence of a number of its pharmacological and structural analogs when performing the general TLC-screening. The presence of specific light absorption in the UV region of the spectrum for atomoxetine makes the UV spectrophotometry method suitable for identification of the antidepressant in toxicological studies.

metry method suitable for identification of the antidepressant in toxicological studies.

Author Biographies

L. Yu. Tomarovska, National University of Pharmacy

teaching assistant of the Physical and Colloid Chemistry Department

S. V. Baiurka, National University of Pharmacy

Doctor of Pharmacy (Dr. habil.), associate professor of the Drug and Analytical Toxicology Department

S. A. Karpushyna, National University of Pharmacy

Candidate of Chemistry (Ph.D.), associate professor of the Drug and Analytical Toxicology Department

References

Garnock–Jones, K. P., Keating, G. M. (2009). Atomoxetine: a review of its use in attention–deficit hyperactivity disorder in children and adolescents. Pediatric Drugs, 11 (3), 203–226. doi: 10.2165/00148581–200911030–00005

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

Treuer, T., Gau, S. S.–F., Méndez, L., Montgomery, W., Monk, J. A., Altin, M., Dueñas, H. J. (2013). A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention–Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability. Journal of Child and Adolescent Psychopharmacology, 23 (3), 179–193. doi:10.1089/cap.2012.0093

Párraga, H. C., Párraga, M. I., Harris, D. K. (2007). Tic Exacerbation and Precipitation during Atomoxetine Treatment in Two Children with Attention–Deficit Hyperactivity Disorder. The International Journal of Psychiatry in Medicine, 37 (4), 415–424. doi: 10.2190/pm.37.4.e

Kasi, P. M., Mounzer, R., Gleeson, G. H. (2011). Cardiovascular side effects of atomoxetine and its interactions with inhibitors of the cytochrome P450 system. Case reports in medicine, 2011, 1–3. doi: 10.1155/2011/952584

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

Lynch, T. (2003). Atomoxetine for ADHD. American Family Physician, 68 (9), 1827–1828.

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

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, 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 (1–2), 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

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

Zhu, H.–J., Wang, J.–S., Donovan, J. L., DeVane, 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, 846 (1–2), 351–354. doi: 10.1016/j.jchromb.2006.08.019

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

Jickells, S., Negrusz, A. (2008). Clarke’s Analytical Forensic Toxicology.London: Pharmaceutical Press, 648.

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.

Rapid Testing Methods of Drugs of Abuse: Manual for Use by National Law Enforcement and Narcotic Laboratory Personnel. (2008). United Nations Office on Drugs and Crime. New York, 111.

Guidance for the Validation of Analytical Methodology and Calibration of Equipment used for Testing of Illicit Drugs in Seized Materials and Biological Specimens.(2009). United Nations Office on Drugs and Crime.New York, 67.

Khizhnichenko, O. V., Huzenko, N. V., Chubenko, O. V. (2011). Farmatsevtychnyi zhurnal, 6, 74–78.

Baiurka, S. V. (2016). Rozrobka metodiv khimiko–toksykolohichnoho analizu likarskykh rechovyn antydepresyvnoi dii. Kharkiv, 547.

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Published

2017-06-16

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Section

Synthesis and Analysis of Biologically Active Substances