Journal
ANALYTICAL BIOCHEMISTRY
Volume 408, Issue 1, Pages 147-156Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2010.09.015
Keywords
Heparin; Glycosaminoglycan; Contaminant; Oversulfated chondroitin sulfate; OSCS; Dermatan sulfate; Mass balance analysis; Heparin lyases
Funding
- National Institutes of Health [HL101721, HL096972]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [RC2HL101721, R01HL096972] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM038060] Funding Source: NIH RePORTER
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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). (C) 2010 Elsevier Inc. All rights reserved.
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