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Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods

Indapamide and dihydralazine can be combined in fixed-dose formulations because of their complementary actions against hypertension. On the other hand, combined formulations present the problem of chemical interactions between the active ingredients, e.g. accelerated degradation of constituents or g...

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Autores principales: Gumieniczek, Anna, Galeza, Justyna, Berecka, Anna, Mroczek, Tomasz, Wojtanowski, Krzysztof, Lipska, Katarzyna, Skarbek, Joanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088757/
https://www.ncbi.nlm.nih.gov/pubmed/35558458
http://dx.doi.org/10.1039/c8ra06707d
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author Gumieniczek, Anna
Galeza, Justyna
Berecka, Anna
Mroczek, Tomasz
Wojtanowski, Krzysztof
Lipska, Katarzyna
Skarbek, Joanna
author_facet Gumieniczek, Anna
Galeza, Justyna
Berecka, Anna
Mroczek, Tomasz
Wojtanowski, Krzysztof
Lipska, Katarzyna
Skarbek, Joanna
author_sort Gumieniczek, Anna
collection PubMed
description Indapamide and dihydralazine can be combined in fixed-dose formulations because of their complementary actions against hypertension. On the other hand, combined formulations present the problem of chemical interactions between the active ingredients, e.g. accelerated degradation of constituents or generation of quite new degradation products. Therefore, the main goal of the present study was to examine the chemical stability of indapamide and dihydralazine, as individuals and as a mixture, to detect potent interactions between both constituents, using FT-IR, HPLC and LC-MS methods. It was clearly shown that both drugs degraded more when they were in the mixture, i.e. indapamide was degraded more under high temperature/high humidity while dihydralazine was more sensitive to UV/VIS light. In solutions, indapamide was sensitive to strong acidic and strong alkaline conditions while dihydralazine degraded at pH ≥ 7. Generally, the process of degradation of indapamide and dihydralazine followed first order kinetics. The fastest degradation of both indapamide and dihydralazine was found at pH ≥ 10. Several degradation products of indapamide and dihydralazine were detected and identified by our LC-MS method. Interactions between both drugs were confirmed by detection of new degradation products of indapamide, i.e. 4-chloro-3-sulfamoylbenzamide and 4-chloro-3-(formylsulfamoyl)-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)benzamide, only in the presence of dihydralazine.
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spelling pubmed-90887572022-05-11 Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods Gumieniczek, Anna Galeza, Justyna Berecka, Anna Mroczek, Tomasz Wojtanowski, Krzysztof Lipska, Katarzyna Skarbek, Joanna RSC Adv Chemistry Indapamide and dihydralazine can be combined in fixed-dose formulations because of their complementary actions against hypertension. On the other hand, combined formulations present the problem of chemical interactions between the active ingredients, e.g. accelerated degradation of constituents or generation of quite new degradation products. Therefore, the main goal of the present study was to examine the chemical stability of indapamide and dihydralazine, as individuals and as a mixture, to detect potent interactions between both constituents, using FT-IR, HPLC and LC-MS methods. It was clearly shown that both drugs degraded more when they were in the mixture, i.e. indapamide was degraded more under high temperature/high humidity while dihydralazine was more sensitive to UV/VIS light. In solutions, indapamide was sensitive to strong acidic and strong alkaline conditions while dihydralazine degraded at pH ≥ 7. Generally, the process of degradation of indapamide and dihydralazine followed first order kinetics. The fastest degradation of both indapamide and dihydralazine was found at pH ≥ 10. Several degradation products of indapamide and dihydralazine were detected and identified by our LC-MS method. Interactions between both drugs were confirmed by detection of new degradation products of indapamide, i.e. 4-chloro-3-sulfamoylbenzamide and 4-chloro-3-(formylsulfamoyl)-N-(2-methyl-2,3-dihydro-1H-indol-1-yl)benzamide, only in the presence of dihydralazine. The Royal Society of Chemistry 2018-10-23 /pmc/articles/PMC9088757/ /pubmed/35558458 http://dx.doi.org/10.1039/c8ra06707d Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Gumieniczek, Anna
Galeza, Justyna
Berecka, Anna
Mroczek, Tomasz
Wojtanowski, Krzysztof
Lipska, Katarzyna
Skarbek, Joanna
Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods
title Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods
title_full Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods
title_fullStr Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods
title_full_unstemmed Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods
title_short Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods
title_sort chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using ft-ir, hplc and lc-ms methods
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088757/
https://www.ncbi.nlm.nih.gov/pubmed/35558458
http://dx.doi.org/10.1039/c8ra06707d
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