Metabolic binding of misonidazole to mouse tissues. Comparison between labels on the ring and side chain, and the production of tritiated water.

The 2-nitroimidazole, misonidazole, is of current interest as an imaging agent for hypoxic regions in tumors and in vascular disease such as stroke. The basis of this technique is the reductive activation and binding of nitroheterocycles which is much more efficient in the absence of oxygen. The appropriate molecular location for an active isotope on the nitroheterocyclic probe depends on the nature of the metabolites retained in tissues after the parent drug has been cleared. Previous studies with tumor cells in vitro indicated that a ring label (2-14C) and a side-chain label (3H) were retained equally efficiently in the acid-insoluble fraction, whereas 1.5 to 3 times more side-chain label was retained in the total pool (acid soluble plus acid insoluble) of metabolites in several normal murine tissues. We show here that the excess side-chain label in six normal tissues, plasma and EMT6 tumors was found entirely in the acid-soluble fraction as a volatile component. This volatile component was tentatively identified as tritiated water. It appeared that, in general, molecular products of misonidazole metabolism were retained in mouse tissues, with the exceptions that a small excess of ring label was found in liver and heart and that tritiated water appeared in the acid-soluble fraction of all tissues. Tritiated water would not be important in imaging studies but could be a factor in studies in which scintillation counting of tritiated nitroheterocyles is used.

Vapor and liquid phase photolysis of the n-butyl ester of 2,4-dichlorophenoxyacetic acid.

The n-butyl ester of 2,4-dichlorophenoxyacetic acid in the liquid and vapor phase was irradiated in a pyrex reactor for 188 hr by ultraviolet light of 300 nm using an intensity similar to that around 300 nm in the solar spectrum. In both phases, the ester was dechlorinated at the ortho position together with simultaneous reduction and Photo-Fries rearrangement to produce volatile photoproducts. Ether bond cleavage to produce chlorophenols, and a Norrish Type II photoprocess, also occurred. A 79% mass balance was accounted for by volatile chlorinated organic residues. HCL gas was also evolved. The production of Cl was also demonstrated in both vapor and liquid phases. The half time of decomposition was around 13 days. The possible effects of the volatile photoproducts on off-target plants were also noted.

2,4-D levels in the South Saskatchewan River in 1973 as determined by GLC method.

2,4-D levels in the South Saskatchewan River near Saskatoon in 1973 at the height of the spraying season, and at harvestime, were determined by a method involving direct glc analysis, ankaline hydrolysis, followed by n-butylation of the liberated free acid after acidification of the alkaline solution, and confirmed by subsequent n-octylation. GC/MS also confirmed the presence of 2,4-D. 2,4-D was detected during the spraying season but not at harvest time or in river mud samples. The average level was ca. 2mug of acid equivalent to 2,4-D per liter of river water at the height of the spraying season.

Gas-liquid chromatography and gas-liquid chromatography combined with mass spectrometry of a butyl ester formulation of (2,4-dichlorophenoxy) acetic acid.

A method is presented for the analysis of (2,4-dichlorophenoxy)acetic acid (2,4-D) in commercial formulations, together with concurrent detection and quantitation of related compounds. The method is based on direct gas-liquid chromatographic (GLC) analysis of the formulation to estimate the various esters present, and on an analysis of the total 2,4-D present involving a prior cleanup, alkaline hydrolysis, acidification and n-butylation steps. This procedure also quantitates any other related acids or phenols present. A step which would extract dioxin impurities is also included. The method was checked by the accepted acid-base estimation of 2,4-D content, GLC, and by subjecting radioactive-labelled herbicide to the above procedures.