title: Heparin identification test and purity test for OSCS in heparin sodium and heparin calcium by weak anion-exchange high-performance liquid chromatography.
abstract: Heparin sodium and heparin calcium, which are widely used as anti-coagulants, are known to potentially contain the natural impurity dermatan sulfate (DS). Recently serious adverse events occurred in patients receiving heparin sodium in the US, and a contaminant oversulfated chondroitin sulfate (OSCS) was found to be a cause of the events. To ensure the quality and safety of pharmaceutical heparins, there is need of a physicochemical identification test that can discriminate heparin from the heparin-related substances as well as a sensitive purity test for OSCS. Recently, HPLC with a strong-anion exchange column was proposed as the methods for identifying heparin and determination of OSCS in heparin sodium. Although this method is convenient and easy to perform, the only column suitable for this purpose is the Dionex IonPac AS11-HC column. In this study, we developed alternative identification test and test for OSCS in both heparin sodium and heparin calcium using a weak anion-exchange column. The identification test allowed for separation of heparin from the impurity DS and contaminant OSCS in a shorter time. The purity test provided enough sensitivity, specificity, linearity, recovery and repeatability for OSCS. We believe that our methods will be useful for quality control of pharmaceutical heparins.
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Hashii
authors.forename: Nana
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Satsuki
authors.initials: S
authors.lastname: Itoh
authors.forename: Yan
authors.initials: Y
authors.lastname: Qin
authors.forename: Naho
authors.initials: N
authors.lastname: Fujita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hattori
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Miyata
authors.forename: Aya
authors.initials: A
authors.lastname: Bando
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hama
authors.forename: Masaki
authors.initials: M
authors.lastname: Kashimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Tatsumi
authors.forename: Kazunori
authors.initials: K
authors.lastname: Mabuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Namekawa
authors.forename: Toru
authors.initials: T
authors.lastname: Sakai
authors.forename: Mio
authors.initials: M
authors.lastname: Hirose
authors.forename: Sei
authors.initials: S
authors.lastname: Dobashi
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Shimahashi
authors.forename: Sadatoshi
authors.initials: S
authors.lastname: Koyama
authors.forename: Susanne Odgaard
authors.initials: SO
authors.lastname: Herr
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kawai
authors.forename: Hikaru
authors.initials: H
authors.lastname: Yoden
authors.forename: Teruhide
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000837:Anion Exchange Resins / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000032:analysis / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D019075:Electrophoresis, Capillary / Q000379:methods; D006493:Heparin / Q000032:analysis* / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D000837:Anion Exchange Resins; C006871:calcium heparin; D006493:Heparin; D002809:Chondroitin Sulfates