Chemical-toxicological determination of felodipine


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Abstract

Aim purpose. The search for optimal conditions for isolating felodipine, its purification and the development of methods for determining felodipine in biological material. Methods. The object of study is felodipine (3-ethyl-5-methyl-4- (2,3-dichlorophenyl) -2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate). Conducted research on the comparative isolation of felodipine from the biomaterial with fluids of organic nature, water and aqueous solutions of various reactions. To perform the experiments, model mixtures of felodipine and crushed liver tissue (particle size 0.2-0.5 cm) with a content of 0.05% of the substance were prepared. Acetone has been proposed as an insulating agent for the recovery of felodipine from biological fluids. For identification and quantification of felodipine in extracts from biological material have been proposed methods of thin layer chromatography (TLC), spectrophotometry, and chromatography - mass spectrometry (GC - MS) Results. It has been established that optimal conditions for the extraction of felodipine from biological material are achieved already with double infusion of a biological object with an insulating agent, if the mass ratio of the insulating liquid and the biomaterial at each stage of infusion is at least 2 : 1, and the duration of infusion is at least 30 minutes. Optimal purification conditions for felodipine were achieved in the macrocolumn of the Silaborus S-18 sorbent 30 μm in height 150 mm and 10 mm in diameter with elution of the substance with acetonitrile-water polar eluant (7 : 3). When the content of felodipine in the amount of 25 mg in 25 g of biological material, the developed method allows to determine 83.91-85.55% in the liver, 83.82-85.63% in the putrefactive liver of this substance. The openable minimum by the method (100 g of a biological object) is: 0.150 mg of the substance in the liver, 0.220 mg in the rotten liver. Conclusion. Thus, the technique can be applied in the practice of chemical-toxicological analysis to study the tissues of fresh and putrefactive corpse organs for the presence of felodipine in them.

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About the authors

L. L Kvachakhiya

Kursk State Medical University

Email: Lekso82@yandex.ru
Ph.D. (Pharm.), Associate Professor of the Department Pharmacology

V. K Shormanov

Kursk State Medical University

Email: R-WLADIMIR@yandex.ru
Dr.Sc. (Phsrm.), Professor of Department of Pharmaceutical, toxicological and analytical Chemistry

D. S Sukhomlinov

Kursk State Medical University

Student, Medical Faculty

References

  1. Felodipine. Available at: https://www.drugbank.ca/drugs /DB01023. Accessed December 25, 2018.
  2. Felodipine. ChemIDplus (a toxnet database). Available at: https://chem.nlm.nih.gov/chemidplus/rn/72509-76-3. Accessed December 25, 2018.
  3. Машковский М.Д. Лекарственные средства. 16-е издание / М.: Новая Волна, 2012; 1216 с.
  4. Felodipine. ChemicalBook. Available at: https://www.che-mical-book.com/ChemicalProductProper-ty_EN_CB4300 661.htm). Accessed December 25, 2018.
  5. Weinstein R.D., Hanlon W.H., Donohue J.P. et al. Solubility of Felodipine and Nitrendipine in Liquid and Supercritical Carbon Dioxide by Cloud Point and UV Spectroscopy // J. Chem. Eng. 2007; 52(1): 256-260.
  6. Pandey M.M., Jaipal A., Kumar A., Malik R., Charde S.Y. Determination of pK(a) of felodipine using UV-Visible spectroscopy // Spectrochimica Acta. Part A, Molecular and Bio-molecular Spectroscopy. 2013; 115: 887-890.
  7. St-Onge M., Dube P.-A., Gosselin S., Guimont C., Godwin J. Treatment for calcium channel blocker poisoning: A systematic review // Clin Toxicol (Phila). 2014; 52(9): 926-944.
  8. Engebretsen K.M., Kaczmarek K.M., Morgan J., Holger J.S. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning // Clinical toxicology. 2011; 49(4): 277-283.
  9. Barnicott L.R., Tarmey N.T., Craig G.R., Thomas S.H. Intravenous lipid emulsion (ILE) therapy for severe felodipine toxicity // Journal of the Intensive Care Society. 2013; 14(4): 346-348.
  10. Deters M., Friesecke S., Hentschel H. Fatal poisoning caused by felodipine // Clin Toxicol. 2010; 48: 281-285.
  11. Lota H., Powell N., Negus R. et al. A case of fatal felodipine overdose // Acute medicine. 2008; 7(1): 39-42.
  12. Yu P., Cheng H., Liu Z. et al. LC-MS/MS determination of felodipine in human plasma // Chinese Journal of Pharmaceutical Analysis. 2012; 32(1): 35-39.
  13. Walash M., Belal F., El-Enany N., Zayed S. Micellar liquid chromatographic determination of felodipine in tablets and human plasma with fluorescence detection: Application to stability studies and content uniformity testing // Analytical methods. 2014; 6(10): 3401-3409.
  14. Miglioranęa L.H., Barrientos-Astigarraga R.E., Schug B.S. et al. Felodipine quantification in human plasma by high-performance liquid chromatography coupled to tandem mass spectrometry // J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2005; 814(2): 217-223.
  15. Chen M., Zhou J., Mei L. et al. Simultaneous Determination of Felodipine and Metoprolol in Beagle Dog Plasma by Online SPE-LC-MS/MS and Its Application in a Pharmacokinetic Study // Analytical Sciences. 2017; 33(7): 755-759.
  16. Квачахия Л.Л., Шорманов В.К. Идентификация нифедипина в биологических жидкостях // Фармация. 2013; 62(8): 16-19.
  17. Шорманов В.К. Квачахия Л.Л. Распределение амлодипина в организме теплокровных животных // Судебномедицинская экспертиза. 2017; 60(1): 23-28.
  18. Шорманов В.К., Пугачёва О.И., Асташкина А.П., Цацуа Е.П. Особенности распределения 2,6-ди-трет-бутил-4-метилгидроксибензола в организме теплокровных животных // Судебно-медицинская экспертиза. 2016; 59(1): 29-34.

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