Measurement of the stability of T-2 toxin in aqueous solution.
Studies were undertaken to determine unambiguously the stability of T-2 toxin in deuterated phosphate-buffered saline solutions in the pD range 5-12. No decomposition was observed after 1 year in samples between pD 5.0 and 6.7; above pD6.7, degradation proceeded via sequential cleavage of the ester side chains to form the series HT-2 toxin to T-2 triol to T-2 tetraol. A transient species believed to be an internal transesterification product of T-2 triol was also detected. Proton NMR was found to be a finely discriminatory technique for the observation and characterization of these species. It was possible for the first time to observe "in real time" the mixture of species, to model the multistage kinetics involved in their interconversion, and to obtain a set of rate constants. The kinetics of the breakdown of T-2 toxin at pD 11.2 were investigated. All reactions were found to be pseudo-first-order with half-lives of 5.4 and 11.7 h for T-2 toxin and HT-2 toxin, respectively. By extrapolation of these results, the half-life of T-2 toxin under quasi-physiological conditions (pD 7.4) was estimated to be about 4 years: this estimate is in broad agreement with the behavior observed in the stability study. Given this remarkable stability of T-2 toxin under pseudophysiological conditions, it was concluded that the contribution of nonenzymatic degradation to the detoxification of T-2 toxin and its metabolites is almost certainly negligible.
College of Graduate Studies and Research, University of Saskatchewan, Saskatoon, Canada.
M J
MJ
Duffy
R S
RS
Reid
D004355:Drug Stability; D006207:Half-Life; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D012996:Solutions; D013605:T-2 Toxin / Q000032:analysis*
D012996:Solutions; D013605:T-2 Toxin