Comprehensive and Updated Study on the Analysis Techniques of

TRIPODI V; LUCANGIOLI S

Heparin: Properties, Uses and Side Effects

Nova Science Publishers, Inc.

Año: 2012; p. 1 - 19

Heparin (Hep) is a linear, highly charged, sulfated polysaccharide that belongs to the glycosaminoglycan family (GAG). Hep has clinically been used for many years in the prevention and initial treatment of thrombosis. Hep is a natural product extracted from animal tissues, most commonly from porcine intestine. As a result of incomplete purification of Hep, other sulfated linear polysaccharides as dermatan sulfate (DS) and chondroitin sulfate (CS) are present in the manufactured product as impurities. The potency of Hep as pharmaceutical agent is defined based on units of biological activity using plasma clotting assays, rather than on the basis of physicochemical properties. However, considerable attention has been focused on analysis of Hep due to a health crisis in 2008 resulting from the contamination of the lots of pharmaceutical Hep with chemically modified chondroitin sulfated (oversulfatedcondroitin sulfate, OSCS) which causes angioedema, hypertension, swelling of the larynx, and in some cases, death. Therefore, different analytical methods have been introduced for government and academic laboratories to assure the quality and safety of pharmaceutical Hep. The elucidation of structure of GAGs has been a challenging task for the analytical laboratories due to their anionic complex structures with high molecular weight and the absence of the strong chromophor groups. Thus, common analytical methodologies often are not suitable for the analysis of Hep impurities and contaminants. Hence, in recent years, different analytical approaches for the analysis of Hep active pharmaceutical ingredient (API) and finished products have been developed by chromatographic techniques as anion exchange HPLC and capillary electrophoresis with varying degrees of success. On the other hand, it has also been developed spectroscopic methods based on analysis by NMR, infrared, Raman and fluorescence as well as bioassays to characterize and identify contaminants of Hep. This chapter describes a comprehensive and updated study on the development techniques for the analysis of Hep content and purity test in pharmaceuticals for human administration.