Development of succinic acid quantitative determination method in the substance of the original compound with antiarrhythmic activity ALM-802S by HPLC

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Introduction. N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine succinate, ALM-802S, is a new pharmacologically active compound synthesized at the Federal State Budgetary Scientific Institution «Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies» as a result of research aimed at screening and creating original medicines with anti-ischemic and antiarrhythmic activity. As part of the research on standardization of the substance ALM-802S, it was decided to specify the content of succinic acid anion in it.

The aim of the work is to develop and validate an analytical procedure for the quantitative determination of succinic acid in the substance of a new compound with antiarrhythmic activity ALM–802S.

Materials and methods. The objects of the study are an experimental sample of the substance ALM–802S and a by-product of its synthesis N1-(2-aminoethyl)-N2-(2,3,4-trimethoxybenzyl)ethane-1,2-diamine trichloride (ALM-848), as well as a sample of the starting material – 2,3,4-trimethoxybenzaldehyde and a sample of succinic acid.. UV spectra of the studied substances were recorded on a Unico 2804 spectrophotometer (United Products and Instruments, USA), measurements were performed in 10 mm quartz cells of the Hellma Analytics (QS) brand. Chromatographic analysis was performed by high performance liquid chromatography on LC-20 Prominence (Shimadzu, Japan) and Infinity 1260 (Agilent Technologies, USA) liquid chromatographs with gradient pumps and variable wavelength spectrophotometric detectors using a Zorbax SB-C18 StableBond chromatographic column in a gradient elution mode.

Results. A procedure for the quantitative determination of succinic acid in the substance of a new compound with antiarrhythmic activity ALM-802S has been developed. The validation of the developed procedure was carried out, the linearity and analytical range of the procedure were determined, the accuracy and precision (repeatability, intermediate precision) of the results were confirmed. The parameters and acceptance criteria for chromatographic system suitability test have been determined.

Conclusions. Using the developed procedure, it was shown that the succinic acid content in the substance ALM-802S corresponds to the theoretical value calculated based on the structural formula of the compound.

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作者简介

D. Kuznetsov

Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies

编辑信件的主要联系方式.
Email: kuznetsov_dn@academpharm.ru
ORCID iD: 0000-0002-0056-4303
SPIN 代码: 6154-6935

Ph.D. (Chem.), Associate Professor, Senior Researcher, Laboratory of Standardization and Quality Control of Medicines, Department of Quality and Technology of Medicines

俄罗斯联邦, Baltiyskaya st., 8, 125315, Moscow

L. Grushevskaya

Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies

Email: grushevskaya_ln@academpharm.ru
ORCID iD: 0000-0002-3794-9661
SPIN 代码: 5599-6685

Dr.Sc. (Pharm.), Head of Laboratory of Standardization and Quality Controlof Medicines, Department of Quality and Technology of Medicines

俄罗斯联邦, Baltiyskaya st., 8, 125315, Moscow

М. Sergeeva

Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies

Email: sergeeva_ms@academpharm.ru
ORCID iD: 0000-0002-7155-6714
SPIN 代码: 5017-2424

Ph.D. (Pharm.), Leading Researcher, Laboratory of Standardization and Quality Control of Medicines, Department of Quality and Technology of Medicines

俄罗斯联邦, Baltiyskaya st., 8, 125315, Moscow

L. Gaevaya

Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies

Email: gaevaya_lm@academpharm.ru
ORCID iD: 0000-0002-0083-6030
SPIN 代码: 7181-6994

Dr.Sc. (Pharm.), Leading Researcher, Laboratory of Standardization and Quality Control of Medicines, Department of Quality and Technology of Medicines

俄罗斯联邦, Baltiyskaya st., 8, 125315, Moscow

Е. Denisenko

Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies

Email: denisenko_ed@academpharm.ru
ORCID iD: 0000-0002-0185-9672
SPIN 代码: 9184-1348

Junior Researcher, Laboratory of Standardization and Quality Control of Medicines, Department of Quality and Technology of Medicines

俄罗斯联邦, Baltiyskaya st., 8, 125315, Moscow

V. Dorofeev

Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies

Email: dorofeev_vl@academpharm.ru
ORCID iD: 0000-0001-7979-8235

Dr.Sc. (Pharm.), Professor, Acting General Director

俄罗斯联邦, Baltiyskaya st., 8, 125315, Moscow

参考

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2. Fig. 1. Structural formulas of ALM-802S and its controlled impurities

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3. Fig. 2. The pKa values of the succinic acid molecule acid sites and the percentage distribution diagrams of the succinic acid possible forms in solution depending on the media pH. Explanations in the text

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4. Fig. 3. UV spectra of ALM-802S, succinic acid, as well as the studied impurities solutions in mobile phase A (concentration of each studied compound is about 0.005 mg/mL)

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5. Fig. 4. Chromatogram of solution of ALM-802S (1), spiked with succinic acid (2) and two process impurities: ALM-848 (3) and 2,3,4-trimethoxybenzaldehyde (4) (the concentration of ALM-802S and 2,3,4-trimethoxybenzaldehyde is about 0.02 mg/mL, the concentration of ALM-848 and succinic acid is about 0.01 mg/mL and 1 mg/mL, respectively)

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6. Fig. 5. Peak area linear correlation to the concentration of succinic acid solutions

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7. Fig. 6. ALM-802S substance sample chromatogram: 1 – ALM-802S; 2 – succinic acid. Concentration of ALM-802S in the test solution is about 1 mg/mL

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