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Deviation from vector addivitity ~0.1 debye occurs only for o-fluoro-and o-iodotoluenes and these are in opposite sense to each other. Until data for the chloro-, bromo-and iodo-toluenes in the vapor phase is available it is felt that a discussion of such deviations as exist is of limited value and would necessarily be somewhat speculative. SummaryThe electric moments of several organic molecules have been determined from gas phase measurements of the dielectric constant at several temperatures and pressures. The results in debyes are: fluorobenzene-1.61, chlorobenzene-1.70, tra-difluorobenzene-1.58, o-dichlorobenzene-2.54, o-fluorotoluene-1.35, wz-fluorotoluene-1.85, ^-fluorotoluene-2.01, diethyl ether-1.14 and methyl ethyl ether-1.22. Durham, N. C.

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The antiparasitic and antibacterial compound, ronidazole (( l-methyl-5-nitroimidazol-2-yl)methyl carbamate), was rapidly absorbed and excreted by the pig after oral administration of 14CH3-labeled drug. Of the total excreted, less than half of the radioactivity was present in the urine. Radioactive residues were ubiquitously distributed in all tissues analyzed. Radioactive residues were present in edible tissues 42 days after dosing and were associated with tissue proteins. The relative depletion rates of different tissues is suggestive of the incorporation of endogeneous metabolites. Liberation of labeled methylamine by acid hydrolysis indicated that as much as 20-30% of the persistent residues retain some chemical relationship to the drug. As the fraction of the persistent residues which liberate methylamine declined with time, at least two general types of residues are present. Further studies using nitric acid oxidation of the residues showed that the fraction containing an intact 1-methyl-5-nitroimidazole nucleus was about 1% of the total residue.Ronidazole [ (l-methyl-5-nitroimidazol-2-yl)methyl carbamate] is a nitroimidazole useful in animal husbandry. Metabolic studies in the turkey have been reported (Rosenblum et al., 1972). These studies showed extensive metabolic degradation with resultant persistent radioactivity in various tissues, especially muscle. Since evolution of 14C02 was reported as 2.5% when the label was at the 2-ring atom and only 0.8% when the CH3 was labeled, 14CH3-labeled ronidazole was used in the current studies except that one animal was dosed with 2-ring-labeled ronidazole. The current studies were designed to determine the distribution of drug and metabolites in edible tissues of the pig, the depletion of radioactive residues with time, and the macromolecular nature of the tissue residue due to ronidazole. Chemical degradation studies designed to determine if the radioactive residues were due exclusively to metabolic degradation to single carbon fragments were carried out. MATERIALS AND METHODS Chemicals.Radiolabeled ronidazole was synthesized in the Merck Sharp & Dohme Research Laboratories. All lots were analyzed for radiochemical purity by paper or thin-layer chromatography and had a radiochemical purity of greater than 98% when used. No single impurity was present in a quantity greater than 0.5%. The specific activity was adjusted for each experiment to a suitable level by dissolving unlabeled and labeled material and either dosing the resultant solution or crystallizing the product before use.14CH3-Labeled ronidazole was synthesized from 14CH30H by treatment with methanesulfonic acid anhydride. The methyl methanesulfonate reacted with 4-nitroimidazole to yield predominantly [methyP4C]-lmethyl-5-nitroimidazole. Reaction with formaldehyde followed by transesterification with methylcarbamate yielded [methyl-14C] ronidazole.Ring 2-labeled ronidazole was synthesized from [2-l4CIimidazole obtained by reaction of ethylenediamine and [14C]formic acid at 500 "C via the usual steps of ...

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