Determination of galactosamine impurities in heparin samples by multivariate regression analysis of their 1H NMR spectra

Qingda Zang, David A. Keire, Richard D. Wood, Lucinda F. Buhse, Christine M.V. Moore, Moheb Nasr, Ali Al-Hakim, Michael L. Trehy, William Welsh

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25 Scopus citations


Heparin, a widely used anticoagulant primarily extracted from animal sources, contains varying amounts of galactosamine impurities. Currently, the United States Pharmacopeia (USP) monograph for heparin purity specifies that the weight percent of galactosamine (%Gal) may not exceed 1%. In the present study, multivariate regression (MVR) analysis of 1H NMR spectral data obtained from heparin samples was employed to build quantitative models for the prediction of %Gal. MVR analysis was conducted using four separate methods: multiple linear regression, ridge regression, partial least squares regression, and support vector regression (SVR). Genetic algorithms and stepwise selection methods were applied for variable selection. In each case, two separate prediction models were constructed: a global model based on dataset A which contained the full range (0-10%) of galactosamine in the samples and a local model based on the subset dataset B for which the galactosamine level (0-2%) spanned the 1% USP limit. All four regression methods performed equally well for dataset A with low prediction errors under optimal conditions, whereas SVR was clearly superior among the four methods for dataset B. The results from this study show that 1H NMR spectroscopy, already a USP requirement for the screening of contaminants in heparin, may offer utility as a rapid method for quantitative determination of %Gal in heparin samples when used in conjunction with MVR approaches.

Original languageEnglish (US)
Pages (from-to)635-649
Number of pages15
JournalAnalytical and Bioanalytical Chemistry
Issue number2
StatePublished - Jan 1 2011

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry


  • Galactosamine impurities
  • Heparin
  • Multivariate regression (MVR)
  • Proton nuclear magnetic resonance ( H NMR)
  • Variable selection

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