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).
- Dermatan sulfate
- Heparin lyases
- Mass balance analysis
- Oversulfated chondroitin sulfate