Monitoring the stability of heparin: NMR evidence for the rearrangement of sulfated iduronate in phosphate buffer

Heparin, a major anticoagulant drug, comprises a complex mixture of motifs. Heparin is isolated from natural sources while being subjected to a variety of conditions but the detailed effects of these on heparin structure have not been studied in depth. Therefore, the result of exposing heparin to a range of buffered environments, ranging pH values from 7 to 12, and temperatures of 40, 60 and 80 degrees C were examined. There was no evidence of significant N-desulfation or 6-O-desulfation in glucosamine residues, nor of chain scission, however, stereochemical re-arrangement of alpha-L-iduronate 2-O-sulfate to alpha-L-galacturonate residues occurred in 0.1 M phosphate buffer at pH 12/80 degrees C. The results confirm the relative stability of heparin in environments like those during extraction and purification processes; on the other hand, the sensitivity of heparin to pH 12 in buffered solution at high temperature is highlighted, providing an important insight for heparin manufacturers.

Automated summary

The study found that heparin is relatively stable during extraction and purification processes, but undergoes structural changes at high temperature and pH 12 in buffered solution. This provides an important insight for heparin manufacturers.