chondroitin-sulfates and Drug-Related-Side-Effects-and-Adverse-Reactions

The recent health care changes and approval of a generic low-molecular-weight heparin (LMWH) by the US Food and Drug Administration (FDA) merit a review of the facts regarding the new and generic anticoagulants. Fatal hypotension from anaphylactoid type reactions following heparin administration was responsible for more than 149 deaths all over the world. Researchers detected a heparin-like semisynthetic contaminant, over-sulfated chondroitin sulfate (OSCS), that appeared to be intentional. Low-molecular-weight heparins are produced using unfractionated heparin and OSCS has been found in various batches of LMWHs. Some newer anticoagulants are claiming to be free from the need to monitor for therapeutic effect and bleeding risk. Therefore, monitoring assays are not being developed and there is no antidote to reverse bleeding. In addition, there are concerns about reproducibility, product variation, and quality. In conclusion, although the generic LMWHs and newer anticoagulants may appear to be effective for qualified indications, their safety remains to be a concern.

Topics: Anaphylaxis; Animals; Anticoagulants; Chondroitin Sulfates; Drug Contamination; Drug-Related Side Effects and Adverse Reactions; Drugs, Generic; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hypotension; Monitoring, Physiologic; United States; United States Food and Drug Administration

Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta1-->3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here.

Topics: Chondroitin Sulfates; Drug Contamination; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Heparin; Humans

Twelve "health foods" products containing chondroitin sulfate (CS) were purchased from the Japanese market and the origin of the CS was investigated by conducting disaccharide compositional analysis after enzymatic depolymerization and by 1H-NMR spectroscopy. Nine of the 12 products had labels indicating that the origin of the CS was shark cartilage. However, two of them were found to contain mammalian CS. Next, we compared the ratio of the sulfate group to the galactosamine residue after the acid hydrolysis of CS. The results suggest that all of the CS from sharks had a ratio of more than 1.0, while the CS from mammals had a ratio of less than 1.0. Since this comparative analysis does not require expensive purified enzyme, it would be an economical way to identify the origin of CS in "health foods." Being able to determine the origin of the ingredients in natural products is very important for ensuring their quality, safety, and efficacy. Therefore, we think that regulatory requirements for accurately indicating the origin of "health foods" and effective enforcement of these requirements are needed.

Topics: Acids; Animals; Carbohydrate Conformation; Carbohydrate Sequence; Cartilage; Chondroitin Sulfates; Chondroitinases and Chondroitin Lyases; Chromatography, High Pressure Liquid; Disaccharides; Drug-Related Side Effects and Adverse Reactions; Food, Organic; Galactosamine; Hydrolysis; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Quality Control; Sharks; Sulfates