Applications of NMR in heparin and low molecular weight heparins

Nuclear magnetic resonance (NMR) is a powerful tool for qualitative and quantitative analysis in the pharmaceutical field. Animal-derived heparin and low molecular weight heparins (LMWHs) are mixtures of polysaccharides widely used as anticoagulants. In this review, studies mainly regarding the application of NMR in heparin and LMWHs in recent years are grouped and discussed. The first part presents an overview of the NMR applications in identification of heparin and LMWHs. Our team participated in the drafting of three LMWHs monographs (enoxaparin, nadroparin and dalteparin), including NMR as identification method, which may promote the revision of the 2025 edition of the Chinese Pharmacopeia. The second part presents the quantification of heparin and LMWHs by NMR. The third part describes the application of NMR combination with multivariate analysis in the distinguishment of different animal origins of heparin, the distinguishment of heparin from different manufacturers, and the determination of the average molecular weight of heparin. The fourth part deals with the determination of the binding interface of the heparin-protein complex by NMR. With the global epidemic COVID-19, proper clinical use of heparin and LMWHs have contributed to reducing the spread and mortality of COVID-19. The fifth part presents the NMR application in the study of the role of heparin in the prevention and treatment of COVID-19. The sixth part reports some examples of NMR applications in heparin-related drug development. Our review has shown that NMR is a versatile tool that not only provides holistic quality control of heparin and LMWHs but is also a promising tool that provides numerous valuable information for potential use. The discussed approaches are recommended to be implemented during the development, production, and quality control process of heparin and LMWHs.