DEVELOPMENT OF A QUANTITATIVE DETERMINATION METHOD OF A NEW QUINOZALININO DERIVATIVE 2-BENZOILAMINO-N-[4-(4,6-DIMETHYLPYRIMIDIN-2-ILSULFAMOIL)-PHENYL]–BENZAMIDE METHOD OF NON-WATER TITRATION

DOI: https://doi.org/10.29296/25877313-2020-04-07
Issue: 
4
Year: 
2020

B.V. Borovskij Ph.D.(Pharm.), Associate Professor, Department of Inorganic, Physical and Colloid Chemistry, Pyatigorsk Medical and Pharmaceutical Institute – Branch of Volgograd State Medical University of the Ministry of Health of Russia E-mail: b.v.borovskiy@pmedpharm.ru N.O. Koval' Post-graduate Student, Department of Inorganic, Physical and Colloid Chemistry, Pyatigorsk Medical and Pharmaceutical Institute – Branch of Volgograd State Medical University of the Ministry of Health of Russia V.A. Kompancev Dr.Sc. (Pharm.), Professor, Department of Inorganic, Physical and Colloid Chemistry, Pyatigorsk Medical and Pharmaceutical Institute – Branch of Volgograd State Medical University of the Ministry of Health of Russia I.P. Kodonidi Dr.Sc. (Pharm.), Professor, Department of Inorganic, Physical and Colloid Chemistry, Pyatigorsk Medical and Pharmaceutical Institute – Branch of Volgograd State Medical University of the Ministry of Health of Russia

In the course of preclinical testing of the substance, research is needed aimed at developing methods of analysis, standardization and the creation of a regulatory document - a pharmacopeia article (FS). To assess the quality of pharmaceutical substances, various quantitative methods are used (titrimetric, chromatographic, spectral). Many methods use standard samples, which are very difficult to obtain when developing methods of a new biologically active substance. The titrimetric methods of pharmaceutical analysis are quite accurate, affordable, simple and do not require complex and expensive equipment and reagents. The purpose of this study is the development and validation of a method for the quantitative determination of the investigated substance - 2-benzoylamino-N- [4-(4,6-dimethylpyrimidin-2-ylsulfamoyl) phenyl] benzamide. During pharmacological studies, anxiolytic, actoprotective and antide-pressant activities were established for this compound. Material and methods. The objects of study were the studied samples of the substance 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsulfamoyl) phenyl] benzamide synthesized at the Department of Organic Chemistry of the Pyatigorsk Medical and Pharmaceutical Institute. Results. The results of the developed procedure for the quantitative determination by a non-aqueous titration method of a new quinosalinone derivative of 2-benzoylamino-N-[4-(4,6-dimethylpyrimidin-2-ylsulfamoyl) phenyl] benzamide are presented. It has been shown that the solvent system is the most protogenic medium for the substance under study. glacial acetic acid  formic acid 10:10 ml. When developing the method using the crystalline violet indicator, the average content of the test substance is 97.12%, the relative error is 2.21%. The potentiometric determination of the end point of the titration showed that the average content of the test substance is 98.67%, the relative error is 1.57%. Conclusion. Thus, we have developed a method for the quantitative determination of a new quinosalinone derivative with pharmacological activity - 2-benzoylamino-N- [4- (4,6-dimethylpyrimidin-2-ylsulfamoyl) phenyl] benzamide. The end point of the titration is determined along with the classic indica-tor crystal violet, it is proposed to carry out using the potentiometric method. A validation assessment of the developed methodology was carried out according to the indicators: linearity, convergence and correctness.

Keywords: 
non-aqueous titration
potentiometry
crystalline violet
glacial acetic acid
chinozalinones

References: 
  1. Aleksandrovskii Yu.A. Etiologicheskie factory I mekhanizmy formirovaniya nevroticheskikh rasstroistv. Psikhiatriya: natsionalnoe rukovodstvo. M.: GEOTAR-Media. 2011. S. 2530.
  2. Polishchyuk Yu.I., Letnikova Z.V. Mnogofaktornyue prichinyu vozniknoveniya i razvitiya nepsikhiatricheskikh depressivnyukh i trevozhnyukh rasstroistv v pozdnem vozraste. Sotsialnaya i klinicheskaya psikhiatriya. 2019; 29(2):8692.
  3. Manvelyan E.A., Manvelyan M.M., Oganesyan E.T. i dr. Novoe N-arilsulfamidnoe proizvodnoe o-benzoilamino-benzoinoi kislotyu, oblzdzyushchee anksioliticheskoi, aktoprotektprnoi i antidepressivnoi aktivnostyu. Eksperimentalnaya i klinicheskaya farmakologiya. 2018; 81(S):151152.
  4. Manvelyan E.A., Manvelyan M.M., Oganesyan E.T. i dr. Antigipoksantnoe deistvie gidroksi- i metoksi-fenilnyukh proizvodnyukh khinazolin-4(3H)-ona. Eksperimentalnaya i klinicheskaya farmakologiya. 2019; 82(4):1619.
  5. Manvelyan E.A., Kodohidi I.P., Oganesyan E.T. i dr. Vliyanie amidov o-benzoilaminobenzoinoi kislotyu, proizvodnyukh predshestvennikov khinazolina-4, yf povedenie samtsov kryus v pripodnyatom krestoobraznom labirinte. Meditsinskii vestnik severnogo Kavkaza. 2014; 9(4):378379.
  6. Patent № 2643356 (RF). Novoe N-arilculfamidnoe proizvodnoe o-benzoilaminobenzoinoi kisloty, obladayushchee ahksioliticheskoi, antiprotektornoi i antidepressivnoi aktivnostyu. E.T. Oganesyan, I.P. Kodohidi, E.A. Manvelyan, V.S. Sochnev, V.Yu. SySa, M.M. Manvelyan. 2018.
  7. Kodonidi I.P. Molekulyarnoe konstruirovanie i tselenapravlennyi sintez N-proizvodnyukh 1,3-diapazona-4: Avtoref. diss. … dokt. farm. nauk: 14.04.02. Pyatigorsk. 2011. 32 s.
  8. Borovskikh B.V., Koval N.O. Izuchenie pokazatelei chistotyu novogo biologicheski aktivnogo soedineniya PMFI-195. Vestnik nauki i obrazovaniya. 2019; 1(55):7882.
  9. Belikov V.G., Borovskikh B.V. Opredelenie 4-amino-3-(piridil-3)-butanovoi kislotyu metodom nevodnogo titrovaniya. Farmatsiya. 2011; 3:810.
  10. Gosudarstvennaya farmakopeya. Izd. XIV. OFS. 1.1.0013.15 «Statisticheskaya obrabotka rezultatov khimicheskogo eksperimenta». Izd. 14-е. M.: FGBU «NTsESMP» Minzdrav Rossii. 2018. Т. 1.289 s.
  11. Rukovodstvo ICN «Validatsiya analiticheskikh metodik». Soderzhanie i metodologiua. Farmatsiya. 2008; 4:310.
  12. Epshtein N.A. Otsenka prigodnosti (validatsiya) VEZhKh-metodik v farmatsevticheskom analize (obzor). Khimiko-farmatsevticheskii zhurnal. 2004; 38(4):4056.