STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS
The aim of the research was to study the stability of a new pharmaceutical substance 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl]quinazoline-4(3Н)-one under stress conditions.Materials and methods. The study was conducted in accordance with the recommendations of the ICH guidelines. The object of the st...
Published in: | Pharmacy & Pharmacology |
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Language: | Russian |
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Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute
2021
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Online Access: | https://doi.org/10.19163/2307-9266-2020-8-4-242-254 https://doaj.org/article/3ff2d458530342f7bd813e73603cf510 |
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ftdoajarticles:oai:doaj.org/article:3ff2d458530342f7bd813e73603cf510 2023-05-15T17:53:45+02:00 STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS T. A. Gendugov A. A. Glushko A. A. Ozerov L. I. Shcherbakova 2021-01-01T00:00:00Z https://doi.org/10.19163/2307-9266-2020-8-4-242-254 https://doaj.org/article/3ff2d458530342f7bd813e73603cf510 RU rus Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute https://www.pharmpharm.ru/jour/article/view/729 https://doaj.org/toc/2307-9266 https://doaj.org/toc/2413-2241 2307-9266 2413-2241 doi:10.19163/2307-9266-2020-8-4-242-254 https://doaj.org/article/3ff2d458530342f7bd813e73603cf510 Фармация и фармакология (Пятигорск), Vol 8, Iss 4, Pp 242-254 (2021) производное хиназолин-4(3н)-она фармацевтическая субстанция стресс-тестирование моделирование стресс-тестов термолиз фотолиз гидролиз высокоэффективная жидкостная хроматография фотостабильность термостабильность gromacs orca Therapeutics. Pharmacology RM1-950 article 2021 ftdoajarticles https://doi.org/10.19163/2307-9266-2020-8-4-242-254 2023-03-19T01:37:21Z The aim of the research was to study the stability of a new pharmaceutical substance 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl]quinazoline-4(3Н)-one under stress conditions.Materials and methods. The study was conducted in accordance with the recommendations of the ICH guidelines. The object of the study was a previously unknown derivative of quinazoline-4(3H)-one: 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl] quinazoline-4(3Н)-one synthesized in Volgograd state medical university. The following laboratory equipment was used: HPLC chromatograph, HPLC-MS, centrifuge, electronic scales, pH meter, thermostat, laboratory filters. The computational experiment was conducted on a computer with an Intel Xeon E3-1230 processor using the programs ORCA 4.1. and GROMACS 2019.Results. The influence of the most unfavorable environmental factors, such as high temperature, light, oxidants, hydrolysis in acidic and alkaline environments, affect the stability of the test substance. The results of the computer-based stability prediction were confirmed by HPLC and HPLC-MS, and the degradation products of the substance under stressful conditions were determined. The conducted studies showed that the test substance is stable to UV radiation at the wavelength of 365 nm, at the elevated temperature (80°C), to the action of oxidants. But it is unstable to hydrolysis: in an alkaline medium of sodium hydroxide 1M, a break in the amide group occurs with the formation of 2-(4-oxoquinazoline-3-yl)acetic acid and 1-phenylpiperazine. And in an acidic environment, hydrochloric acid 1M is also destroyed, but it is significantly reduced, presumably due to the protonation and stabilization of tertiary nitrogen atoms in the molecule.Conclusion. The conducted research makes it possible to conclude that the test substance 3-[2-(4-phenyl-1-of piperazino)-2-oxoethyl]quinazoline-4(3Н)-one is stable to aggressive environmental factors, with the exception of hydrolysis in an alkaline environment that will be further considered in the preparation of regulatory ... Article in Journal/Newspaper Orca Directory of Open Access Journals: DOAJ Articles Pharmacy & Pharmacology 8 4 242 254 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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Russian |
topic |
производное хиназолин-4(3н)-она фармацевтическая субстанция стресс-тестирование моделирование стресс-тестов термолиз фотолиз гидролиз высокоэффективная жидкостная хроматография фотостабильность термостабильность gromacs orca Therapeutics. Pharmacology RM1-950 |
spellingShingle |
производное хиназолин-4(3н)-она фармацевтическая субстанция стресс-тестирование моделирование стресс-тестов термолиз фотолиз гидролиз высокоэффективная жидкостная хроматография фотостабильность термостабильность gromacs orca Therapeutics. Pharmacology RM1-950 T. A. Gendugov A. A. Glushko A. A. Ozerov L. I. Shcherbakova STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS |
topic_facet |
производное хиназолин-4(3н)-она фармацевтическая субстанция стресс-тестирование моделирование стресс-тестов термолиз фотолиз гидролиз высокоэффективная жидкостная хроматография фотостабильность термостабильность gromacs orca Therapeutics. Pharmacology RM1-950 |
description |
The aim of the research was to study the stability of a new pharmaceutical substance 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl]quinazoline-4(3Н)-one under stress conditions.Materials and methods. The study was conducted in accordance with the recommendations of the ICH guidelines. The object of the study was a previously unknown derivative of quinazoline-4(3H)-one: 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl] quinazoline-4(3Н)-one synthesized in Volgograd state medical university. The following laboratory equipment was used: HPLC chromatograph, HPLC-MS, centrifuge, electronic scales, pH meter, thermostat, laboratory filters. The computational experiment was conducted on a computer with an Intel Xeon E3-1230 processor using the programs ORCA 4.1. and GROMACS 2019.Results. The influence of the most unfavorable environmental factors, such as high temperature, light, oxidants, hydrolysis in acidic and alkaline environments, affect the stability of the test substance. The results of the computer-based stability prediction were confirmed by HPLC and HPLC-MS, and the degradation products of the substance under stressful conditions were determined. The conducted studies showed that the test substance is stable to UV radiation at the wavelength of 365 nm, at the elevated temperature (80°C), to the action of oxidants. But it is unstable to hydrolysis: in an alkaline medium of sodium hydroxide 1M, a break in the amide group occurs with the formation of 2-(4-oxoquinazoline-3-yl)acetic acid and 1-phenylpiperazine. And in an acidic environment, hydrochloric acid 1M is also destroyed, but it is significantly reduced, presumably due to the protonation and stabilization of tertiary nitrogen atoms in the molecule.Conclusion. The conducted research makes it possible to conclude that the test substance 3-[2-(4-phenyl-1-of piperazino)-2-oxoethyl]quinazoline-4(3Н)-one is stable to aggressive environmental factors, with the exception of hydrolysis in an alkaline environment that will be further considered in the preparation of regulatory ... |
format |
Article in Journal/Newspaper |
author |
T. A. Gendugov A. A. Glushko A. A. Ozerov L. I. Shcherbakova |
author_facet |
T. A. Gendugov A. A. Glushko A. A. Ozerov L. I. Shcherbakova |
author_sort |
T. A. Gendugov |
title |
STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS |
title_short |
STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS |
title_full |
STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS |
title_fullStr |
STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS |
title_full_unstemmed |
STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS |
title_sort |
study of the stability of the substance 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl]quinazoline-4(3н)-one under stressful conditions |
publisher |
Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute |
publishDate |
2021 |
url |
https://doi.org/10.19163/2307-9266-2020-8-4-242-254 https://doaj.org/article/3ff2d458530342f7bd813e73603cf510 |
genre |
Orca |
genre_facet |
Orca |
op_source |
Фармация и фармакология (Пятигорск), Vol 8, Iss 4, Pp 242-254 (2021) |
op_relation |
https://www.pharmpharm.ru/jour/article/view/729 https://doaj.org/toc/2307-9266 https://doaj.org/toc/2413-2241 2307-9266 2413-2241 doi:10.19163/2307-9266-2020-8-4-242-254 https://doaj.org/article/3ff2d458530342f7bd813e73603cf510 |
op_doi |
https://doi.org/10.19163/2307-9266-2020-8-4-242-254 |
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Pharmacy & Pharmacology |
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8 |
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4 |
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242 |
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