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DETERMINATION OF RESIDUAL ORGANIC SOLVENTS IN THE SUBSTANCE 6- [4-METOXI-3- (1H-PYRAZOL-1-ILMETHYL) BENZYL]-1,11-DIMETHYL-3,6,9-TRIAZATRICYCLO [7.3.1.1] TETRADEKAN-4,8,12-TRION BY GLC METHOD

DOI: https://doi.org/10.29296/25877313-2021-10-05
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Issue: 
10
Year: 
2021

G.E. Brkich Ph.D. (Pharm.), Head of the Center for Pharmaceutical Technologies, Institute of Translational Medicine and Biotechnology, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University) (Moscow, Russia) E-mail: brkich@yandex.ru N.V. Pyatigorskaya Dr.Sc. (Pharm.), Professor, Deputy Director of the Institute of Translational Medicine and Biotechnology, Head of the Department of Industrial Pharmacy of the Institute of Professional Education, Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University) (Moscow, Russia)

Relevance. Determination of the content of organic solvents is subject to those pharmaceutical substances and excipients, in the production of which organic solvents are used or formed at any stage of production. During the synthesis of the substance 6- [4-methoxy-3- (1H-pyrazol-1-ylmethyl) benzyl] -1,11-dimethyl-3,6,9-triazatricyclo [7.3.1.1] tetradecane-4,8,12-trione, a volatile organic solvent chloroform is used, which belongs to the 2nd class of toxicity, due to its natural toxicity, the residual content of which must be determined after the completion of the technological process of ob-taining a pharmaceutical substance. This article is devoted to the development and validation of a method for the quantitative determination of the re-sidual organic solvent - chloroform by GLC in the pharmaceutical substance 6- [4-methoxy-3- (1H-pyrazol-1-ylmethyl) benzyl] -1,11-dimethyl-3,6, 9-triazatricyclo [7.3.1.1] tetradecane-4,8,12-trione, the content of which must not exceed 60 ppm according to General Pharmacopoeia Monograph 1.1.0008.15 «Residual organic solvents» and ICH Q3C (R3) «Impurities: guide to residual organic solvents». Aim. Development and validation of a method for the determination of residual organic solvents in the pharmaceutical substance 3,7-diazabicyclo[3.3.1]nonane derivative. Material and methods. The object of research is a pharmaceutical substance with the chemical name IUPAC 6-[4-methoxy-3- (1H-pyrazol-1-ylmethyl) benzyl] -1,11-dimethyl-3,6,9-triazatricyclo[7.3.1.1]tetradecane -4,8,12-trione, based on the 3,7-diazabicyclo[3.3.1]nonane derivative, belonging to the class of AMPA receptor modulators (AMPAkins). The studies were performed using a gas chromatography-mass spectrometer - Agilent 6890N / 5973 and an automatic headspace sampler - Agilent 7679А. Carrier gas - helium, chromatographic column DV-624 (30 mx 0.32 mm inner diameter x 1.8 μm - film thickness). Results. A method for the determination of the residual organic solvent of chloroform in the pharmaceutical substance 3,7-diazabicyclo[3.3.1]nonane derivative has been developed and validated by GLC. Conclusions. This technique can be used to determine residual organic solvents in the substance 3,7-diazabicyclo[3.3.1]nonane derivative and will be included in the draft regulatory documentation for the pharmaceutical substance.
Keywords: 
chloroform
residual organic solvents
3
7-diazabicyclo[3.3.1]nonane derivative

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