led to the conclusion that the contamination was deliberate

Differentiation was improved with the use of principal component analysis, a powerful statistical tool that allows the identification of patterns in any dataset and highlights their similarities and differences. This approach has been used to extract relationships from many forms of spectra and numerical data related to GAGs. In the present paper, we investigate the possibility of a simpler UVbased Begacestat technique – scanning UV spectroscopy, combined with PCA, as a potential method for the assessment of heparin purity. The more technically demanding and expensive NMR technique was also employed as an external control of the effectiveness of the method. The issue of heparin impurities has been well-known since 1955, when the first paper was published regarding the identification of phosphate in heparin preparations. Ginsenoside-F5 Subsequently, mixtures of glycosaminoglycans and other organic and inorganic impurities were found in pharmaceutical heparin preparations. With the outbreak of BSE this matter resurfaced, however, none of these problems led to a major heparin recall across the globe. In 2008, health authorities in the United States received several alerts regarding acute hypersensitivity reactions due to the use of heparin in patients undergoing dialysis. These reports led to a major recall, first in the USA and then Europe, of heparin batches, heparin coated medical devices, and lock flush-injections that used heparin as the active pharmaceutical ingredient. By June of the same year Guerrini and colleagues had identified and characterized the major contaminant in heparin batches as an oversulfated chrondroitin sulfate, a compound that does not exist naturally, which led to the conclusion that the contamination was deliberate. Subsequently, several other groups published papers on the same subject using a wide variety of methods. More recently, the contaminant was claimed to compromise not only OSCS but a mixture of other chemically sulfated GAGs, probably arising from waste generated throughout the heparin production process. Also, the mechanism in which the OSCS contaminant caused the anaphylactoid responses was characterized, and recently how these semi-synthetic GAGs activate the complement system and how they affect GAG-dependent cell signaling pathways have also been investigated. The methods capable of identifying impurities and suitable for the assessment of heparin purity and safety are often based on NMR, which is a very time consuming and expensive technique since it relies on technically complicated procedures using expensive machines that are not available in many laboratories, a fact that makes it difficult for all but the best equipped laboratories to monitor heparin preparations on a large scale. Moreover, the presence of significant amounts of DS in drugs constituted by GAG mixtures raises the limit of detection.

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