Nuclear Magnetic Resonance Spectrometry Combined with Chemometric Methods of Data Processing as a Method for the Study of the Composition and Properties of Heparin Preparations

The composition and properties of heparin preparations are studied by NMR spectrometry. Approaches to the determination of the most important heparin quality indicators (biological origin and manufacturing company) based on multivariate modeling of the NMR profile of a sample are considered. Chemometric modeling of two-dimensional (2D) NMR spectra (DOSY, HSQC, HMBC) by the principal component and discriminant analysis is performed to increase the efficiency of analysis. Multivariate regression models (partial least squares) are built for the first time to determine the average molecular weight of heparin. Quantitative NMR spectrometry is applied to the determination of water, calcium and sodium cations, and also chloride and acetate anions in heparin preparations. The determination of all characteristics requires five consecutive measurements by NMR (H-1, D-2, Cl-35, Na-23, and 2D DOSY) spectrometry and one sample preparation. The duration of analysis of one sample, including measurements and signal processing, takes no more than 20 min. The proposed approach is universal and can be used in the analysis of other medicinal preparations.