CHOICE OF AN EFFECTIVE METHOD OF BIOLOGICAL OBJECTS PREPARATION FOR RESEARCH OF PHARMACOKINETICS OF MONOMECAINE

DOI: https://doi.org/10.29296/25877313-2020-04-06
Issue: 
4
Year: 
2020

Yu.N. Karpenko Ph.D. (Pharm.), Associate Professor, Department of Toxicological Chemistry, Perm State Pharmaceutical Academy; LLC «Parma Clinical» E-mail: karpenko_pfa@mail.ru N.D. Saidov Post-graduate Student, Department of Pharmacy, Tajik National University (Dushanbe, Republic of Tajikistan) E.A. Bulgakova Ph.D. (Pharm.), Department of Toxicological Chemistry, Perm State Pharmaceutical Academy T.L. Malkova Dr.Sc. (Pharm.), Full Professor, Head of the Department of Toxicological Chemistry, Perm State Pharmaceutical Academy

Monomecaine is an original biologically active compound with antiarrhythmic action, synthesized in Perm State Pharmaceutical Academy. At the stage of preclinical pharmacokinetic research, among other things, the processes of distribution of a potential drug in the organs and tissues of laboratory an-imals are studied. The purpose of the work was to select optimal conditions for isolation of monomecaine from biological objects using the liquid-liquid extraction method. Material and methods. The research was carried out on model mixtures of homogenized liver of laboratory animals with the addition of 25, 50, 100 mcg monomecaine. During the development of methods of isolating the substance at the stage of infusion tested polar sol-vents: water and acetonitrile, at the stage of extraction - organic solvents: chloroform, methyltretbutyl ether. The quantitative determination of monomecaine in the extractions was carried out by high perfomance liquid chromatography on the chromatograph "LC-20 Prominence" (Shimadzu) with a diode matrix detector. Results. In the course of the experiment it was found that monomecaine is most effectively extracted by infusion of biological object with acetonitrile with subsequent extraction of chloroform. The degree of extraction of monomecaine from liver tissue was over 80%. Conclusions. The developed method provides a high degree of extraction of the investigated substance, is notable for its reproducibility, simplicity of execution and can be used in preclinical pharmacokinetic studies.

Keywords: 
antiarrhythmic agents
monomecaine
high-performance liquid chromatography
liquid-liquid extraction
pharmacokinetic studies

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