Mass balance analysis of contaminated heparin product

Zhenling Liu, Zhongping Xiao, Sayaka Masuko, Wenjing Zhao, Eric Sterner, Vinod Bansal, Jawed Fareed, Jonathan Dordick, Fuming Zhang, R. J. Linhardt Robert J.

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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).

Original languageEnglish
Pages (from-to)147-156
Number of pages10
JournalAnalytical Biochemistry
Volume408
Issue number1
DOIs
StatePublished - 1 Jan 2011
Externally publishedYes

Keywords

  • Contaminant
  • Dermatan sulfate
  • Glycosaminoglycan
  • Heparin
  • Heparin lyases
  • Mass balance analysis
  • OSCS
  • Oversulfated chondroitin sulfate

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