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Development and validation of a stability-indicating HPLC assay method for determination of ethacrynic acid in solution formulation. HPLC-MS identification of hydrolytic and oxidative degradation products

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Degradation products of ethacrynic acid
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Submitted   Jul 19, 2020
Published   Aug 31, 2020
Issue    Vol 2 No 1 (2020)
DOI   10.25082/JPBR.2020.01.005

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Mónika Kuzma corresponding author
Institute of Pharmaceutical Chemistry, University of Pécs, Rókus Str. 2, Pécs 7624, Hungary & Department of Forensic Medicine, University of Pécs, Medical School, Szigeti Str. 12, Pécs 7624, Hungary
Veronika Murányi
Institute of Pharmaceutical Chemistry, University of Pécs, Rókus Str. 2, Pécs 7624, Hungary
Mátyás Mayer
Department of Forensic Medicine, University of Pécs, Medical School, Szigeti Str. 12, Pécs 7624, Hungary
Zsuzsanna Rozmer
Institute of Pharmaceutical Chemistry, University of Pécs, Rókus Str. 2, Pécs 7624, Hungary
Pál Perjési
Institute of Pharmaceutical Chemistry, University of Pécs, Rókus Str. 2, Pécs 7624, Hungary

Abstract

An isocratic stability-indicating HPLC assay method was developed to quantitate ethacrynic acid in solution formulations. Utilizing the method, the main hydrolytic, and one of the oxidative degradation products could be separated. The structure of the separated degradation products was confirmed by negative ion-mode HPLC-MS. The hydrolytic results confirmed the previously reported sequence of the formation of the dimeric Michael adduct. One new oxidative metabolite has been identified. The validated analytical method can be used to quantitate ethacrynic acid in a solution formulation in the 0.5-500 µg/ml concentration range.

Keywords
forced degradation, hydrolytic degradation products, oxidative degradation products, michael addition reaction, stability-indicating HPLC method, HPLC-MS

Article Details

Supporting Agencies
This work was supported by the National Office of Research and Technology, “Pázmány Péter program” (RET-II 08/2005), the European Union, co-financed by the European Social Fund (EFOP-3.6.1.-16-2016-00004).
How to Cite
Kuzma, M., Murányi, V., Mayer, M., Rozmer, Z., & Perjési, P. (2020). Development and validation of a stability-indicating HPLC assay method for determination of ethacrynic acid in solution formulation. HPLC-MS identification of hydrolytic and oxidative degradation products. Journal of Pharmaceutical and Biopharmaceutical Research, 2(1), 131-144. https://doi.org/10.25082/JPBR.2020.01.005
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

References

  1. Schultz EM, Cragoe EJ, Bicking JB, et al. Alpha, betaunsaturated ketone derivatives of aryloxyacetic acids, a new class of diuretics. Journal of Medicinal and Pharmaceutical Chemistry, 1962, 5(3): 660-662. https://doi.org/10.1021/jm01238a030
  2. Gussin RZ and Cafruny EJ. Renal sites of action of ethacrynic acid. Journal of Pharmacology and Experimental Therapeutics, 1966, 153(1): 148-158. https://jpet.aspetjournals.org/content/153/1/148
  3. Cannon PJ and Laragh JH. Studies of mechanism of action and effectiveness of ethacrynic acid, a new and unique diuretic agent. Annals of Internal Medicine, 1964, 60(4): 738- 739. https://doi.org/10.7326/0003-4819-60-4-738_3
  4. Vardanyan R and Hruby V. Synthesis of Best-Seller Drugs. Chapter 21 - Diuretics, Acedemic Press, Amsterdam, 2016, 317-327. https://doi.org/10.1016/B978-0-12-411492-0.00021-3
  5. Valdes RM, Huff MO, El-Masri MA, et al. Effect of ethacrynic acid on sodium pump alpha isoforms in SHSY5Y cells. Bipolar Disorders, 2003, 5(2): 123-128. https://doi.org/10.1034/j.1399-5618.2003.00001.x
  6. Markadieu N and Delpire E. Physiology and pathophysiology of SLC12A1/2 transporters, Pfl¨ugers Archiv - European Journal of Physiology, 2014, 466: 91-105. https://doi.org/10.1007/s00424-013-1370-5
  7. Molnar J and Somberg JC. The clinical pharmacology of ethacrynic acid. American Journal of Therapeutics, 2009, 16(1): 86-92. https://doi.org/10.1097/MJT.0b013e318195e460
  8. Klaassen CD and Fitzgerald TJ. Metabolism and biliary excretion of ethacrynic acid. Journal of Pharmacology and Experimental Therapeutics, 1974, 191(3): 548-556. http://jpet.aspetjournals.org/content/191/3/548
  9. Tingey DP, Ozment RR, Schroeder A, et al. The effect of intracameral ethacrynic acid on the intraocular pressure ofliving monkeys. American Journal of Ophthalmology, 1992, 113(6): 706-711. https://doi.org/10.1016/S0002-9394(14)74799-3
  10. Epstein DL, Roberts BC and Skinner LL. Nonsulfhydrylreactive phenoxyacetic acids increase aqueous humor outflow facility. Investigative Ophthalmology and Visual Science, 1997, 38(8): 1526-1534. https://iovs.arvojournals.org/article.aspx?articleid=21808_14
  11. Epstein DL, Hooshmand LB and Epstein MPM. Thiol adducts of ethacrynic acid increase outflow facility in enucleated calf eyes. Current Eye Research, 1992, 11(3): 253- 258. https://doi.org/10.3109/02713689209001776
  12. Melamed S, Kotas-Neumann R, Barak A, et al. The effect of intracamerally injected ethacrynic acid on intraocular pressure in patients with glaucoma. American Journal of Ophthalmology, 1992, 113(5): 508-512. https://doi.org/10.1016/S0002-9394(14)74721-X
  13. Medipolisz South Transdanubian Regional Knowledge Centre (RET). http://medipolisz.pte.hu/index.html
  14. Blessy M, Patel RD, Prajapati PN, et al. Development of forced degradation and stability indicating studies of drugs - A review. Journal of Pharmaceutical Analysis, 2014, 4(3): 159-165. https://doi.org/10.1016/j.jpha.2013.09.003
  15. Singh S and Bakhsi M. Guidance on conduct of stress tests to determine inherent stability of drugs. Pharmaceutical Technology on-line, 2000. https://pdfs.semanticscholar.org/fce4/347f5ddbc12ac1f74d9f7e7ae6db3be2336b.pdf
  16. Carstensen JT and Rhodes CT. (Eds.) 2000, Drug Stability. Principles and Practices. 3rd ed, Marcel Dekker, New York. ISBN: 0-8247-0376-6
  17. Bakshi M and Singh S. Development of validated stabilityindicating assay methods - critical review. Journal of Pharmaceutical and Biomedical Analysis, 2002, 28(6): 1011- 1040. https://doi.org/10.1016/S0731-7085(02)00047-X
  18. Baertschi SW, Alsante K and Reed RA. (Eds.) 2011, Pharmaceutical Stress Testing. Predicting Drug Degradation. 2nd ed, Taylor and Francis Group, New York. https://doi.org/10.3109/9781439801802
  19. Reynolds DW. Forced degradation of pharmaceuticals. American Pharmaceutical Review, 2004, 7: 56-61.
  20. Sneha A, Ramya GG, Sneha S, et al. Stability studies of pharmaceutical products. World Journal of Pharmaceutical Research, 2019, 8(1): 479-492. https://doi.org/10.20959/wjpr20191-13872
  21. Smela MJ. Regulatory considerations for stability indicating analytical methods in drug substance and drug product testing. American Pharmaceutical Review, 2005, 8: 51-54.
  22. Soni NR. 2018, Stability Indicating Analytical Methods (SIAMs): Pharmaceutical Analysis. Scholars’ Press. ISBN: 978-6202305327.
  23. Cohen EM. Polarographic determination of ethacrynic acid. Journal of Pharmaceutical Science, 1971, 60(11): 1702- 1704. https://doi.org/10.1002/jps.2600601126
  24. Goerlitzer K and Hoebbel G. Zur Gehaltsbestimmung von Etacryns¨aure Ph. Eur. III. Archive der Pharmazie, 1979, 312(7): 631-632. https://doi.org/10.1002/ardp.19793120715
  25. Auterhoff H and Thinnes J. Nachweisreaktionen der Etacryns¨aure. Archive der Pharmazie, 1979, 312(12): 1037- 1042. https://doi.org/10.1002/ardp.19793121212
  26. Yarwood RJ, Phillips AJ, Dickinson NS, et al. The kinetics of degradation of ethacrynic acid in aqueous solution. Drug Development and Industrial Pharmacy, 1983, 9(1-2): 35-41. https://doi.org/10.3109/03639048309048543
  27. Yarwood RJ, Moore WD and Collett JH. Liquid chromatographic analysis of ethacrynic acid and degradation products in pharmaceutical systems. Journal of Pharmaceutical Science, 1985, 74(2): 220-223. https://doi.org/10.1002/jps.2600740226
  28. Yarwood RJ, Moore WD and Collett JH. The influence of the ammonium ion on the stability of ethacrynic acid in aqueous solution. Journal of Pharmaceutical and Biomedical Analysis, 1987, 5(4): 369-378. https://doi.org/10.1016/0731-7085(87)80043-2
  29. Koechel DA, Gisvold O and Cafruny EJ. Synthesis and pharmacology of an epoxide derivative of ethacrynic acid. Journal of Medicinal Chemistry 1971, 14(7): 628-629. https://doi.org/10.1021/jm00289a016
  30. Datey KK, Deshmukh SN, Dalvi CP, et al. Hepatocellular damage with ethacrynic acid. British Medical Journal, 1967, 3: 152-153. https://doi.org/10.1136/bmj.3.5558.152
  31. ICH Harmonised tripartite guideline. Validation of analytical procedures: Text and methodology Q2(R1). https://database.ich.org/sites/default/files/Q2%28R1%29%20Guideline.pdf
  32. Gupta VD. Quantitation of ethacrynic acid by high pressure liquid chromatography. Drug Development and Industrial Pharmacy, 1982, 8(6): 869-882. https://doi.org/10.3109/03639048209022131
  33. European Pharmacopoeia (Ph. Eur.) 10th Edition. EDQM, 2019, 2563. https://www.edqm.eu/en/european-pharmacopoeia-ph-eur-10th-edition
  34. United States Pharmacopoeia 30 - National Formulary 25, 2007, 2087. https://www.uspnf.com/official-text/proposal-statuscommentary/usp-30-nf-25
  35. Voith B, Spahn-Languth H and Mutschler E. New specific and sensitive HPLC-assays for ethacrynic acid and its main metabolite - the cysteine conjugate - in biological material. Journal of Pharmaceutical and Biomedical Analysis, 1995, 13(11): 1373-1382. https://doi.org/10.1016/0731-7085(95)01558-3
  36. Tirona RG and Pang KS. Bimolecular glutathione conjugation kinetics of ethacrynic acid in rat liver: in vitro and perfusion studies. Journal of Pharmacology and Experimental Therapeutics, 1999, 290(3): 1230-1241. http://jpet.aspetjournals.org/content/290/3/1230
  37. Zendelovska D and Stafilov T. Sample preparation and RPHPLC determination of diuretics in human body fluids. Acta Pharmaceutica, 2006, 56: 115-142. http://acta.pharmaceutica.farmaceut.org/11506.pdf
  38. Muszy´nski P, Brodowska MS and Paszko T. Occurrence and transformation of phenoxy acids in aquatic environment and photochemical methods of their removal: a review. Environmental Science and Pollution Research, 2020, 27: 1276- 1293. https://doi.org/10.1007/s11356-019-06510-2