Mass balance analysis of contaminated heparin product
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Authors
Liu, Zhenling
Xiao, Zhongping
Masuko, Sayaka
Zhao, Wenjing
Sterner, Eric
Bansal, Vinod
Fareed, Jawed
Dordick, Jonathan
Zhang, Fuming
Linhardt Robert J., R. J.
Issue Date
2011-01-01
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
A quantitative analysis of a recalled contaminated lot of heparin sodium injection U.S. Pharmacopeia (USP) was undertaken in response to the controversy regarding the exact nature of the contaminant involved in the heparin (HP) crisis. A mass balance analysis of the formulated drug product was performed. After freeze-drying, a 1-ml vial for injection afforded 54.8±0.3 mg of dry solids. The excipients, sodium chloride and residual benzyl alcohol, accounted for 11.4±0.5 and 0.9±0.5 mg, respectively. Active pharmaceutical ingredient (API) represented 41.5±1.0 mg, corresponding to 75.7 wt% of dry mass. Exhaustive treatment of API with specific enzymes, heparin lyases, and/or chondroitin lyases was used to close mass balance. HP represented 30.5±0.5 mg, corresponding to 73.5 wt% of the API. Dermatan sulfate (DS) impurity represented 1.7±0.3 mg, corresponding to 4.1 wt% of API. Contaminant, representing 9.3±0.1 mg corresponding to 22.4 wt% of API, was found in the contaminated formulated drug product. The recovery of contaminant was close to quantitative (95.6-100 wt%). A single contaminant was unambiguously identified as oversulfated chondroitin sulfate (OSCS).
Description
Analytical Biochemistry, 408, 147-156
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Mass balance analysis of contaminated heparin product, Z. Liu, Z. Xiao, S. Masuko, W. Zhao, E. Sterner, V. Bansal, J. Fareed, J. S. Dordick, F. Zhang, R. J. Linhardt, Analytical Biochemistry, 408, 147-156, 2011.
Publisher
Elsevier
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
10960309
32697
32697