RESUMEN
Due to problems, especially anaphylactoid reactions, raised by impure unfractionated heparin the quality assessment of heparin has to be reconsidered. Neither the USP nor the European Pharmacopoeia are able to guarantee the purity of heparin, i.e., the limitation of oversulfated chondroitin sulfate (OSCS) which was found to be the reason for the allergic adverse effects. In the first run the regulatory authorities ask for 1H NMR spectroscopic and capillary electrophoretic measurements in order to characterize the impurity profile of heparin. Using an optimized 1H NMR method the limit of detection for OSCS was found to be 0.1%. In addition, it is possible to reliably quantify both OSCS and dermatan sulfate (DS), the latter being an indicator of poor purification of the unfractionated heparin. Screening of more than 100 heparin samples collected from international markets revealed a high number of samples containing substantial amounts of DS and a number of samples containing OSCS in an amount higher than 0.1%.
Asunto(s)
Anticoagulantes/análisis , Heparina de Bajo-Peso-Molecular/análisis , Espectroscopía de Resonancia Magnética , Anticoagulantes/química , Sulfatos de Condroitina/química , Dermatán Sulfato/química , Heparina de Bajo-Peso-Molecular/química , Estructura MolecularRESUMEN
NMR spectroscopy being a primary ratio method of measurement is highly suitable to evaluate the quality of drugs. NMR spectroscopy can be used for the identification of a drug substance, the identification and quantification of impurities arising from the synthesis pathway and degradation, or residual solvents as well as the determination of the content in the assay. This review gives an overview of the application of quantitative NMR spectroscopy in International Pharmacopoeias and for licensing purposes.