Decomposition and quality control considerations in biological work with fecapentaene preparations
| Autor: | Andrews Aw, T. Anjo, Bradford Ww rd, Wu Pp, Peter J. Donovan, L. Ohannesian, Elmer J. Reist, Larry K. Keefer, Anthony J. Streeter, P R Sheffels |
|---|---|
| Rok vydání: | 1989 |
| Předmět: |
Quality Control
Antioxidant Mutagenicity Tests medicine.medical_treatment Vitamin E Biological activity Esters General Medicine Polyenes Toxicology Diacetyl Decomposition Dithiothreitol chemistry.chemical_compound chemistry Nucleophile Solubility medicine Organic chemistry Spectrophotometry Ultraviolet Carcinogen Chromatography High Pressure Liquid Mutagens |
| Zdroj: | Chemical research in toxicology. 2(3) |
| ISSN: | 0893-228X |
| Popis: | Solutions of synthetic fecapentaene 12 (FP-12) intended for carcinogenicity studies were found to decompose extremely rapidly during customary dosage procedures. Apparent half-lives as short as 15 min were observed. While rates and even the qualitative course of decomposition were surprisingly variable in replicate experiments, high concentration and exposure to air were confirmed to be especially important destabilizing influences. The results suggested a primary role for a radical decomposition mechanism in the presence of atmospheric oxygen. Consistent with this hypothesis, FP-12 solutions were significantly stabilized by the radical chain-breaking antioxidant vitamin E. On the other hand, dithiothreitol greatly destabilized FP-12, presumably because of its nucleophilicity. The diacetyl diester of FP-12 was more soluble than the parent diol, but its decomposition rates in the presence and absence of vitamin E were similar to those of unesterified FP-12. Ultraviolet irradiation of an all-trans-FP-12 solution decreased its concentration by 70% in 0.5 min. The mutagenicities of the decomposition/isomerization products of FP-12, as studied in Salmonella typhimurium tester strain TA 100, ranged from negligible to comparable with all-trans-FP-12 itself. It is concluded that unchecked decomposition of fecapentaene preparations can profoundly affect biological tests therewith. While this can be largely controlled through the use of rigorous precautions, including protection from air, light, nucleophiles, and acids as well as selection of the lowest concentration compatible with the application at hand, the data argue strongly for inclusion of appropriate quality control measures in all future dosing operations to prove that the biological activity reported is that of the fecapentaene itself rather than that of a decomposed dosing solution. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|