Chondroitin sulfate: are the purity and the structural features well assessed? A review on the analytical challenges

Animal origin chondroitin sulfate is employed as anti-inflammatory drug and food supplement against anti-osteoarthritis, but also as antioxidant, antitumor, anticoagulant, and immune-regulatory agent or as biomaterial in tissue engineering scaffolds and in drug-delivery systems. As its biological properties depend on the structural characteristics, multi-analytical approaches are necessary to correlate specific features of its heterogenic composition to the different bioactivities. This is of paramount importance to assess the efficacy of pharmaceuticals and food supplements, beyond safety quality control. This review would address the issue of chondroitin sulfate characterization according to the Pharmacopeia testing monograph point of view giving an update of the analytical novelties reported in the last ten years that might be employed for the product testing and releasing on the market. Not-instrumental (e.g. colorimetric assays) and instrumental techniques, most of them coupling diverse chromatographic separation methods with spectroscopic and spectrometry detection techniques, mono and bi-dimensional NMR approaches, are compared as tools to evaluate identity, titer, purity grade, monosaccharide and disaccharide composition, averaged molecular weight and viscosity, charge and sulfate content, impurities and related substances including the presence of other glycosaminoglycans.