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New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method

Hydrochloride of 10-{2-hydroxy-3-[N,N-bis-(2-hydroxyethyl)amino]propyl}-2-trifluoromethylphenothiazine (Flu-A) is a analogue of neuroleptic fluphenazine. Flu-A exhibits anti-multidrug resistance, antimutagenic, proapoptopic, and cancer-chemopreventive activities in screening studies. To define ident...

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Autores principales: Sobczak, Agnieszka, Teżyk, Artur, Szyndlarewicz, Joanna, Ziarniak, Jan, Świątek, Piotr, Malinka, Wiesław
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628186/
https://www.ncbi.nlm.nih.gov/pubmed/29051697
http://dx.doi.org/10.1007/s00044-017-1944-4
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author Sobczak, Agnieszka
Teżyk, Artur
Szyndlarewicz, Joanna
Ziarniak, Jan
Świątek, Piotr
Malinka, Wiesław
author_facet Sobczak, Agnieszka
Teżyk, Artur
Szyndlarewicz, Joanna
Ziarniak, Jan
Świątek, Piotr
Malinka, Wiesław
author_sort Sobczak, Agnieszka
collection PubMed
description Hydrochloride of 10-{2-hydroxy-3-[N,N-bis-(2-hydroxyethyl)amino]propyl}-2-trifluoromethylphenothiazine (Flu-A) is a analogue of neuroleptic fluphenazine. Flu-A exhibits anti-multidrug resistance, antimutagenic, proapoptopic, and cancer-chemopreventive activities in screening studies. To define identity, quality, and purity of new active substance it is necessary to develop a appropriate analytical method and to establish a degradation profile. Thus, a stability-indicating reversed-phase high-performance liquid chromatography method was developed and validated for quantitative determination of Flu-A in the presence of its degradation products generated under stress conditions. The compound was subjected to oxidation, photolysis, and degradation in aqueous solutions (neutral and acidic), and solid state according to the International Council for Harmonisation Guidelines. The method was also found to be suitable for intermediate and accelerated studies and for the evaluation of kinetic mechanism of Flu-A degradation in aqueous solutions (pH 5.1–7.5, 353 K). The structures of main potential degradation products were established using high-performance liquid chromatography-Electrospray Ionization-mass spectrometry method.
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spelling pubmed-56281862017-10-17 New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method Sobczak, Agnieszka Teżyk, Artur Szyndlarewicz, Joanna Ziarniak, Jan Świątek, Piotr Malinka, Wiesław Med Chem Res Original Research Hydrochloride of 10-{2-hydroxy-3-[N,N-bis-(2-hydroxyethyl)amino]propyl}-2-trifluoromethylphenothiazine (Flu-A) is a analogue of neuroleptic fluphenazine. Flu-A exhibits anti-multidrug resistance, antimutagenic, proapoptopic, and cancer-chemopreventive activities in screening studies. To define identity, quality, and purity of new active substance it is necessary to develop a appropriate analytical method and to establish a degradation profile. Thus, a stability-indicating reversed-phase high-performance liquid chromatography method was developed and validated for quantitative determination of Flu-A in the presence of its degradation products generated under stress conditions. The compound was subjected to oxidation, photolysis, and degradation in aqueous solutions (neutral and acidic), and solid state according to the International Council for Harmonisation Guidelines. The method was also found to be suitable for intermediate and accelerated studies and for the evaluation of kinetic mechanism of Flu-A degradation in aqueous solutions (pH 5.1–7.5, 353 K). The structures of main potential degradation products were established using high-performance liquid chromatography-Electrospray Ionization-mass spectrometry method. Springer US 2017-06-15 2017 /pmc/articles/PMC5628186/ /pubmed/29051697 http://dx.doi.org/10.1007/s00044-017-1944-4 Text en © The Author(s) 2017 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Sobczak, Agnieszka
Teżyk, Artur
Szyndlarewicz, Joanna
Ziarniak, Jan
Świątek, Piotr
Malinka, Wiesław
New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method
title New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method
title_full New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method
title_fullStr New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method
title_full_unstemmed New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method
title_short New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method
title_sort new fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628186/
https://www.ncbi.nlm.nih.gov/pubmed/29051697
http://dx.doi.org/10.1007/s00044-017-1944-4
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