Identification of a novel structure in heparin generated by sequential oxidative-reductive treatment
Research article published in Analytical chemistry (2012)
Abstract
Unfractionated heparin is isolated from animal organs, predominantly porcine intestinal mucosa, and goes through an extensive process of purification before it can be used for pharmaceutical purposes. While the structural microheterogeneity of heparin is predominantly biosynthetically imprinted in the Golgi, subsequent steps involved in the purification and manufacture of commercial heparin can lead to the introduction of additional modifications. Postheparin crisis of 2008, it has become increasingly important to identify what additional structural diversity is introduced as a function of the purification process and thus can be determined as being heparin-related, as opposed to being an adulterant or contaminant, e.g., oversulfated chondroitin sulfate. Our study focuses on the identification of a previously unreported structure in heparin that arises due to specific steps used in the manufacturing process. This structure was initially observed as a disaccharide peak in a complete enzymatic digest of heparin, but its presence was later identified in the NMR spectra of intact heparin as well. Structural elucidation experiments involved isolation of this structure and analysis based on multidimensional NMR and liquid chromatography coupled with mass spectrometry (LC-MS). Heparin was also subjected to specific chemical reactions to determine which steps in the manufacturing process are responsible for this novel structure. Our results allowed for the definitive assignment of the structure of this novel process-related modification and enabled an identification of the putative steps in the process that give rise to the structure.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Unfractionated heparin is isolated from animal organs, predominantly porcine intestinal mucosa, and goes through an extensive process of purification before it can be used for pharmaceutical purposes.
Warum dies für die Hirudotherapie relevant ist
Diese Forschungsarbeit identifiziert eine zuvor nicht beschriebene strukturelle Modifikation in unfraktioniertem Heparin, die aus spezifischen Schritten des Herstellungs- und Aufreinigungsprozesses nach der Heparin-Krise von 2008 resultiert. Mittels mehrdimensionaler NMR-Spektroskopie und LC-MS ordneten die Autoren die Struktur dieser neuartigen prozessbedingten Modifikation eindeutig zu und identifizierten die mutmaßlichen Herstellungsschritte, die dafür verantwortlich sind; dies trägt dazu bei, genuine Heparin-bedingte Heterogenität von Verfälschungsmitteln wie übersulfatiertem Chondroitinsulfat zu unterscheiden. Das Abstract gibt die genaue chemische Natur der Herstellungsschritte über die Bezeichnung ‚spezifische Schritte' hinaus nicht an. Blutegel, Hirudotherapie oder aus Blutegeln stammende Antikoagulanzien werden nicht erwähnt, sodass die Studie keine direkte Relevanz für den ASH-Bereich aufweist.
Zitation
Identification of a novel structure in heparin generated by sequential oxidative-reductive treatment
Beccati D et al. · Analytical chemistry, 2012
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