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Investigation of the effect of heating on the chemistry and antifactor Xa activity of enoxaparin
Citation
Patel, R and Narkowicz, CK and Jacobson, GA, Investigation of the effect of heating on the chemistry and antifactor Xa activity of enoxaparin, Journal of Pharmaceutical Science, 98, (5) pp. 1700 - 1711. ISSN 0022-3549 (2009) [Refereed Article]
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Abstract
The objective of this study was to investigate the effects of heating on the chemistry, physical properties and antifactor Xa activity of enoxaparin. Samples of enoxaparin heated at 70°C lost 27% of their initial AFXa activity after 8 h, then activity increased to 94% of the initial activity over the next 4 h. Activity then decreased to 84% of control after 48 h and further to 80% of control over 22 days. The initial activity loss correlated with desulfation as demonstrated by sulfate and amine analysis. Fragmentation of oligosaccharides occurred, as demonstrated by reducing capacity and capillary electrophoresis analysis. Individual enoxaparin fractions obtained by high performance size exclusion chromatography were analysed. Early eluting fractions, containing aggregated oligosaccharides, increased in concentration following heating. Up to 65% of sulfate was lost from some fractions, containing hexa- and octa-saccharides, after 8 h, corresponding with decreased activity. Low mass oligosaccharide fractions increased in concentration and had increased activity between 8 and 12 h. Reversed-phase ion-interaction HPLC analysis supported these findings. Deca-, dodeca- and tetradeca-saccharides were resistant to thermal degradation. Desulfation, fragmentation and aggregation occur during the heating of enoxaparin and result in the initial rapid loss, recovery and subsequent gradual loss of activity.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | AFXa activity enoxaparin stability heating sulfate fragmentation aggregation |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Pharmaceutical sciences |
| Objective Division: | Health |
| Objective Group: | Public health (excl. specific population health) |
| Objective Field: | Public health (excl. specific population health) not elsewhere classified |
| UTAS Author: | Patel, R (Dr Rahul Patel) |
| UTAS Author: | Narkowicz, CK (Dr Christian Narkowicz) |
| UTAS Author: | Jacobson, GA (Professor Glenn Jacobson) |
| ID Code: | 53238 |
| Year Published: | 2009 |
| Web of Science® Times Cited: | 14 |
| Deposited By: | Pharmacy |
| Deposited On: | 2008-11-14 |
| Last Modified: | 2010-06-29 |
| Downloads: | 5 View Download Statistics |
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