Study of the stability of the substance 3-[2-(4-phenyl-1- piperazino)-2-oxoethyl]quinazoline-4(3н)-one under stressful conditions
- Authors: Gendugov T.A.1, Glushko A.A.1, Ozerov A.A.2, Shcherbakova L.I.1
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Affiliations:
- Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
- Volgograd State Medical University
- Issue: Vol 8, No 4 (2020)
- Pages: 242-254
- Section: Articles
- URL: https://ogarev-online.ru/2307-9266/article/view/111645
- DOI: https://doi.org/10.19163/2307-9266-2020-8-4-242-254
- ID: 111645
Cite item
Abstract
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 documents for this pharmaceutical substance.
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##article.viewOnOriginalSite##About the authors
Tembot A. Gendugov
Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
Author for correspondence.
Email: timbirlei2008@rambler.ru
ORCID iD: 0000-0002-7447-8328
Post-graduate student of the Department of Inorganic, Physical and Colloidal Chemistry
Russian Federation, 11, Kalinin Ave., Pyatigorsk, 357532Aleksandr A. Glushko
Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
Email: alexander.glushko@lcmmp.ru
ORCID iD: 0000-0002-1715-0350
Candidate of Sciences (Pharmacy), Associate Professor of the Department of Inorganic, Physical and Colloidal Chemistry
Russian Federation, 11, Kalinin Ave., Pyatigorsk, 357532Alexander A. Ozerov
Volgograd State Medical University
Email: prof_ozerov@yahoo.com
ORCID iD: 0000-0002-4721-0959
Doctor of Sciences (Chemistry), Professor, the Head of the Department of Pharmaceutical and Toxicological Chemistry
Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131Larisa I. Shcherbakova
Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
Email: shcherbakovali@mail.ru
ORCID iD: 0000-0002-7806-2805
Candidate of Sciences (Pharmacy), Associate Professor, the Head of the Department of Inorganic, Physical and Colloidal Chemistry
Russian Federation, 11, Kalinin Ave., Pyatigorsk, 357532References
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