E.A. Arianova, M.N. Bogachuk, O.I. Perederyaev

Prevention and treatment of thrombosis, as well as disturbances of microcirculation are important for clinical practice. For the treatment of these diseases it is necessary to use anticoagulants. One of the most common anticoagulant is heparin and its derivatives, in particular low-molecular weight heparin (LMWH). The process of production and the source of heparin have great importance for the properties of LMWH, as well as influence the pharmacological effect and safety of its derivatives. In the case of heparin, a naturally occurring final product may contain a different set of polysaccharide residues, depending on the species chosen and the method for obtaining tissue LMWH. The most detailed methods for determining the authenticity of LMWH are presented in the European and British pharmacopoeias. With respect to these medications listed regulations are similar. Common Article to LMWH in the section definition of authenticity involves the use of nuclear magnetic resonance, the ratio of activities of anti-factor Xa to anti-factor II-a, exclusion chromatography and tested for sodium or calcium (depending on the drug). The definition of the ratio of activity of anti-factor Xa to anti-factor II-a, and exclusion chromatography are used for quantitative assessment. To determine the range of molecular weights of LMWH in pharmacopoeial studies typically use size exclusion high performance liquid chromatography (HPLC) and capillary electrophoresis, which has not yet found a full-fledged application in its pharmacopoeia studies. One of the most important indicators of the quality of LMWH is the determination of related impurities. In foreign pharmacopoeias content of free nitrogen, calcium, sodium, sulfate ions to the ratio of carboxylate ions, toxic chemicals or bacterial endotoxin are standardized, as well as loss in weight on drying. However, in general article on the pharmaceutical LMWH no tests otherwise impurities, in particular to Chondroitin Sulfate. The increasing significance of LMWH and the problems of assessing their quality and safety have been widely discussed. However, should be noted that the used methods have its own problems and limitations, hence the lack of common approaches for assessing their quality and safety of LMWH. For the analysis of LMWH are used the following methods: (a) HPLC and capillary electrophoresis for qualitative and quantitative determination of both LMWH and impurities in it, (b) biological methods for evaluating the authenticity and the quantitative determination of LMWH. Analysis of scientific publications shows that the composition of LMWH and the possible impurities is not fully understood. Of particular concern is the fact that the final composition of the drug based on LMWH is influenced by method of processing and source. In particular, a variety of materials and methods of preparation contribute to the emergence of a large number of impurities difficult to detect. This leads to the developing a comprehensive approach to quality and safety of LMWH, which includes qualitative and quantitative analysis of LMWHs, its biological activity, as well as analysis of known and potential impurities.