An assessment of polydispersed species in unfractionated and low molecular weight heparins by diffusion ordered nuclear magnetic resonance spectroscopy method.

The primary goal of this project is to extend a (1)H NMR based method, which combines elements of separation on the basis of molecular size with the information specific to (1)H-1D NMR, to the assessment of the heparin contaminant oversulfated chondroitin sulfate (OSCS) and process related impurity dermatan sulfate (DS), and their polydisperse degradation products in samples of unfractionated heparins (UFHs) and low molecular weight heparins (LMWHs) used as the active pharmaceutical ingredients (APIs) in finished pharmaceutical products. The method has been briefly introduced by us in a recent contribution (vide infra). We propose a labelling of the N-acetyl peaks in the (1)H NMR spectra of the UFHs and LMWHs with the parameter D(i), the translational diffusion coefficient available from DOSY NMR. It is shown how DOSY can be applied for screening lots of unfractionated and depolymerised heparins for obtaining molecular size information for heparins and any impurities when using (1)H NMR. The evidence has been presented that title method can be applied as a routine means for assessment of the OSCS and DS contaminants and the polydisperse chemical entities present in the UFHs and LMWHs used as the APIs in heparin pharmaceuticals. Copyright (c) 2010 Elsevier B.V. All rights reserved.