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Decomposition and quality control considerations in biological work with fecapentaene preparations.

Abstract：

: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.

journal_name

Chem Res Toxicol

journal_title

Chemical research in toxicology

authors

Streeter AJ,Donovan PJ,Anjo T,Ohannesian L,Sheffels PR,Wu PP,Keefer LK,Andrews AW,Bradford WW 3rd,Reist EJ

doi

10.1021/tx00009a007

subject

Has Abstract,Author List Incomplete

pub_date

1989-05-01 00:00:00

pages

162-8

issue

eissn

0893-228X

issn

1520-5010

journal_volume

pub_type

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Decomposition and quality control considerations in biological work with fecapentaene preparations.