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

Aleksandra Kozlowski, Edwin A. Yates, Johannes P Roubroeks, Kristoffer Tømmeraas, Flemming H. Larsen, Alan Smith, Gordon Morris

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 °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 α-L-iduronate 2-O-sulfate to α-L-galacturonate residues occurred in 0.1 M phosphate buffer at pH 12/80 °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.

Original languageEnglish
Article number120649
Number of pages9
JournalCarbohydrate Polymers
Volume308
Early online date11 Feb 2023
DOIs
Publication statusPublished - 15 May 2023

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