Heparin identification test and purity test for OSCS in heparin sodium and heparin calcium by weak anion-exchange high-performance liquid chromatography.
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.
Hashii
Noritaka
N
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Kawasaki
Nana
N
Itoh
Satsuki
S
Qin
Yan
Y
Fujita
Naho
N
Hattori
Toshiaki
T
Miyata
Kazuyoshi
K
Bando
Aya
A
Sekimoto
Yuko
Y
Hama
Takeshi
T
Kashimura
Masaki
M
Tatsumi
Masashi
M
Mabuchi
Kazunori
K
Namekawa
Hiroshi
H
Sakai
Toru
T
Hirose
Mio
M
Dobashi
Sei
S
Shimahashi
Hirotoshi
H
Koyama
Sadatoshi
S
Herr
Susanne Odgaard
SO
Kawai
Kenzo
K
Yoden
Hikaru
H
Yamaguchi
Teruhide
T
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
D000837:Anion Exchange Resins; C006871:calcium heparin; D006493:Heparin; D002809:Chondroitin Sulfates