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Professor A.P. Sinitsin (1), PhD; V.P. Khotchenkov (1), PhD; Professor B.A. Rudoy (2), PhD; Yu.G. Kazaishvili (2), PhD 1-Federal Research Center of Biotechnology, Russian Academy of Sciences; 33, Leninsky Prospect, Build. 2, Moscow 119071, Russian Federation; 2-NEARMEDIC PLUS; 12, Aircraft Designer Mikoyan St., Moscow 125252, Russian Federation

Introduction. Kagocel (12-mg tablets) has been designed on the basis of an oxidized cellulose polymer with grafted chemically modified molecules of the natural polyphenol gossypol. When this natural highly biologically active polyphenol is in a bound state, it loses its toxicity, by maintaining its beneficial pharmacological properties. The manufacture of Kagocel ensures thorough removal of unbounded free gossypol residues and control of the presence of the latter. Lack of toxic effects of Kagocel has been confirmed by preclinical studies. In addition, the safety of the drug can be proved by the fact that free gossypol cannot be released from the active substance of the drug in the human body under the influence of digestive juices. Objective: to estimate the content of free gossypol in Kagocel after exposure to standard model environments, such as human gastric and intestinal juice simulants, as well as after incubation of the drug in the medium containing active microbial cellulase. Material and methods. The investigation object was 12-mg tablets of Kagocel. The highly sensitive method, namely: high-performance liquid chromatography with mass spectrometric detection (HPLC-MS) was used to monitor and quantify free gossypol as part in the model media. Results. The highly sensitive and highly specific HPLC-MS procedure was developed and validated to determine minimal quantities of residual free gossypol in Kagocel (12-mg tablets). The procedure allows reliable detection of free gossypol at solution concentrations in the range of 0.005 to 2.500 µg/ml. The content of traces as free gossypol in the medium after 24-hour incubation in standard gastric and intestinal juice simulants, as well as after exposure to microbial cellulase did not increase. Conclusion. The release and accumulation of free gossypol do not occur after prolonged incubation of Kagocel in both simulation and microbial cellulase-containing environments.

model media
high-performance liquid chromatography

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