Instrumental methods in analytical studies of indolocarbazole derivatives with antitumor activity

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Abstract

Background. The development of innovative national antitumor drugs remains an ultimately important task. Among the new drugs, which selectively affect tumors, indolo [2,3-a] carbazole – N-glycosides LCS-1208 and LCS-1269, synthesized using an original technique at the Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, are of essential interest. The paper presents possible options of instrumental analytical methods for identification of differences in the physical chemical features of structurally similar compounds LCS-1208 and LC S-1269. These methods may be used for establishing experimentally justified standards of quality for the standardization of the compounds as pharmaceutical substances.

Aim. To study the physical chemical features and to develop methods for the qualitative and quantitative analysis of LCS-1208 and LCS-1269.

Materials and methods. The study involved modern instrumental methods of analysis, such as polarimetry, ultraviolet spectroscopy, infrared spectroscopy, proton magnetic resonance spectroscopy spectroscopy, high performance liquid chromatography (HPLC), and HPLC with the tandem mass spectrometric detection (HPLC–MS / MS).

Results. Significant differences in the physical chemical features of the original N-glycosides LCS-1208 and LCS-1269 were determined using modern instrumental analytical methods.

The authors present the results verifying the structure of each of these compounds. The methods for qualitative and quantitative analysis of these compounds were developed in the study. The HPLC validation was performed for the LCS-1269 quantification method. The study showed the compliance of the obtained validation characteristics with the criteria approved by the Russian State Pharmacopoeia XV Ed and Pharmacopoeia of the Eurasian Economic Union. The authors determined the structure of impurities in LCS-1269 samples and proposed a method for their quantitative determination.

Conclusion. Structures of indolo [2,3-a] carbazole derivatives LCS-1208 and LCS-1269 were confirmed and shown to be reliably distinguishable. Impurity structures from the final LHS-1269 synthesis step were identified. HPLC methods for quantifying LCS-1208 and LCS-1269 were developed.

About the authors

Elena V. Ignateva

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Author for correspondence.
Email: chem_pharm@ronc.ru
ORCID iD: 0000-0002-9200-4492
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Irina V. Yartseva

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: chem_pharm@ronc.ru
ORCID iD: 0000-0002-8818-7812
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Dmitry A. Kozin

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: chem_pharm@ronc.ru
ORCID iD: 0000-0003-1125-1932
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Dmitriy V. Gusev

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: chem_pharm@ronc.ru
ORCID iD: 0000-0003-0218-8265
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Lydia V. Ektova

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: chem_pharm@ronc.ru
ORCID iD: 0000-0002-3987-6072
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

Zoya S. Shprakh

N. N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: chem_pharm@ronc.ru
ORCID iD: 0000-0003-3034-750X
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

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