STUDY OF THE DEGRADATION PROFILES OF RAMIPRIL AND HYDROCHLOROTHIAZIDE AS A STAGE IN THE DEVELOPMENT OF METHOD FOR DETERMINATION IMPURITIES IN THE COMBINED DOSAGE FORM
DOI:
https://doi.org/10.11603/mcch.2410-681X.2023.i4.14367Keywords:
related substances, ramipril, hydrochlorothiazide, tablets, liquid chromatographyAbstract
Introduction. It is important for drug manufacturers, to guarantee the quality of the drug product during the shelf life. Therefore, quality control methods should be suitable stability testing.
The aim of the study – to investigate the degradation profile of ramipril and hydrochlorothiazide and establish the possibility of using the developed method for the simultaneous determination of impurities of both components in the combined preparation.
Research Methods. The research used standard samples of ramipril, hydrochlorothiazide and ramipril impurities A, B, C, D (USP RS), class A reagents, 2.5 mg tablets of Ramipril and Ramipril with Hydrochlorothiazide 10 mg/12.5 mg. The samples were analyzed on a liquid chromatograph with an Agilent 1260 diode array detector. An Inertsil ODS-3 column (4.6×150×3 μm) was used; mobile phase A – 0.2 g/l sodium hexanesulfonate solution (pH 2.7); mobile phase B: acetonitrile; mobile phase speed 1.5 ml/min; detection wavelength – 210 nm; column temperature – 45 °C, gradient elution mode.
Results and Discussion. We have previously developed an HPLC method for the determination of ramipril in tablets, which we tested in our studies to study the degradation profiles. Under the influence of stress factors on the placebo drug, no additional peaks were detected. Alkaline hydrolysis has the most significant effect on the degradation of both ramipril and hydrochlorothiazide. Degradation products of hydrochlorothiazide have retention times from 2 to 5 min, ramipril from 10 to 20 min. That is, the developed methodology allows to determine impurities of both active substances.
Conclusions. The developed analytical procedure can provide simultaneous determination of impurities of ramipril and hydrochlorothiazide while stability testing of the combined dosage form.
References
https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_3
https://pubchem.ncbi.nlm.nih.gov/compound/Ramipril
European Pharmacopoeia. (2022). European Pharmacopoeia (11st edn.). Retrieved from: https://www.edqm.eu/en/european-pharmacopoeia-ph.-eur.-11th-edition (accessed on 22 March 2023).
Pharmacopeia, U. S., & Pharmacopeia, U. S. (2021). National Formulary, The United States Pharmacopeial Convention. Inc., Rockville, MD. Retrieved from: https://www.uspnf.com (accessed on 22 March 2023).
De Diego, M., Godoy, G., Mennickent, S., Olivares, M., & Godoy, R. (2010). Stress degradation studies of ramipril by a validated stability-indicating liquid chromatographic method. Journal of the Chilean Chemical Society, 55(4), 450-453. DOI: https://doi.org/10.4067/S0717-97072010000400008
Lakshmi, K.S., & Sivasubramanian, L. (2010). A stability indicating HPLC method for the simultaneous determination of valsartan and ramipril in binary combination. Journal of the Chilean Chemical Society, 55(2), 223-226. DOI: https://doi.org/10.4067/S0717-97072010000200017
Yb, M.L. (2013). Stability indicating RP-HPLC method for determination of ramipril in pure and pharmaceutical formulation. Asian Journal of Pharmaceutical and Clinical Research, 158-161.
Mahajan, A.A., Thaker, A.K., & Mohanraj, K. (2012). LC, LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation. Journal of the Brazilian Chemical Society, 23, 445-452. DOI: https://doi.org/10.1590/S0103-50532012000300010
Bhagwate, S., & Gaikwad, N.J. (2013). Stability indicating HPLC method for the determination of hydrochlorothiazide in pharmaceutical dosage form. Journal of Applied Pharmaceutical Science, 3(2), 088-092.
Rao, A.L., Varma, D., & Dinda, S.C. (2012). Stability indicating RP-HPLC method for simultaneous Determination of telmisartan and hydrochlorothiazide in Pharmaceutical dosage form. Int Journal of Pharmaceutical, Chemical and Biological Sciences, 2(3), 382-391.
Typlynska, K., Kondratova, Y., & Logoyda, L. (2023). Development of Methods of Quality Control of the Tablets “Ramipril”. Scientia Pharmaceutica, 91(2), 21. DOI: https://doi.org/10.3390/scipharm91020021
Snyder, L.R., Kirkland, J.J., & Dolan, J.W. (2011). Introduction to modern liquid chromatography. John Wiley & Sons.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Medical and Clinical Chemistry
This work is licensed under a Creative Commons Attribution 4.0 International License.