The absorption, tissue distribution, metabolism, and excretion of moxidectin, a new endectocide for the control of internal and external parasites in cattle and sheep, was studied in cattle. Following a single subcutaneous dose of 14C-and 2H-labeled moxidectin of 0.2 mg/kg of body weight, highest 14C residues were present in abdominal fat (898,636, and 275 ppb) and back fat (495,424, and 186 ppb) a t 7, 14, and 28 days posttreatment, respectively. Lower residues were detected in liver (109, 77, and 31 ppb), kidney (42,38, and 13 ppb), and loin muscle (21,10, and 4 ppb), respectively. The administered radioactivity was excreted primarily in the feces, with only 3 % of the dose being eliminated in the urine. The HPLC/14C profiles of the residues extracted from the tissues, fat, and feces were qualitatively similar and showed moxidectin was the major component of the residue. Only two metabolites were present that were more than 5 % (2 ppb) of the total liver residues after 28 days. These were identified as the C-29/30 and the C-14 monohydroxymethyl metabolites by LC/MS and LC/MS/MS analysis of the metabolites isolated from the feces. Proton NMR analysis of the authentic compounds prepared in-uitro from cattle liver microsomal incubation and rat liver homogenate incubation with 14C-labeled moxidectin confirmed the mass spectral results. By LC/MS and LC/MS/MS, several other mono-and dihydroxylated and 0-demethylated metabolites were also identified.Moxidectin is a semisynthetic derivative of nemadectin (Asato and France, 1990), a macrocyclic lactone produced by fermentation in a culture of Streptomyces cyanogriseus.
ZULALIAN, GATTERDAMalously with the glucosyl bromide to give N-alkylation or phenyl alkylation was eliminated, for either possibility would result in a product containing a phenolic group. The absence of an aromatic hydroxyl was demonstrated by determining the uv spectra in neutral and in basic solution. Whereas the absorption maxima of 1 and 2 were shifted in the presence of sodium hydroxide, no shift occurred in the uv maxima of 5, 6, or indeed chlorpropham itself.The Michael synthesis is known to yield ß-rather than -glucosides. Confirmation of the ß configuration of compounds 3, 4, 5, and 6 was obtained by determining their specific optical rotations. These rotations, ranging from -39°to -69°, were in the range of values of the ß isomers of known substituted phenyl glucosides and their tetraacetates (-103°t o +45°) rather than in the range of the corresponding a isomers (+137°to + 212°) (Bonner et al., 1952). The susceptibility of 5 and 6 to hydrolysis by the enzyme, /3-glucosidase, also indicates ß configuration. Efforts to confirm the configuration of 3, 4, 5, and 6 by their nmr spectrum were unsuccessful. The H-l' doublet could not be observed because of signal overlap and difficulties with radiofrequency saturation.The mass spectrum of 3 showed mass peaks corresponding to those reported by Still and Mansager (1972) for a sample of acetylated chlorpropham conjugate from soybeans.ed. His procedure involved the reduction of commercially available p-nitrophenyl-/3-glucuronide, followed by reaction with isopropyl chloroformate. ACKNOWLEDGMENTThe author is indebted to Derek Horton of Ohio State University for many helpful suggestions on these syntheses and to the following PPG Industries staff for their part in this work: Kenneth Dress (uv determinations), James Gregory (synthesis of 1), Robert Pfost (mass spectra interpretation), Robert Shupe (ir and nmr determinations), Albert Strong (synthesis of 2), and Jerome Wiedmann (enzymatic hydrolysis studies).
The imidazolinone compounds are a new class of herbicides which are environmentally safe and effective at very low application rates. Because of the shared imidazolinone ring structure amongst several herbicides, generic antibodies were prepared which recognized all the compounds in this class (1). These antibodies are useful not only for developing immunoassays for the detection of low levels of residues in soil or in plant extracts, they are also useful for preparing antibody affinity columns used for sample clean-up in metabolism and residue studies. Imidazolinone-compound containing extracts from wheat plant, corn grain, corn fodder, goat urine, and goat kidney tissue were tested on the antibody columns. It was found that the analytes were bound to the antibody column after some simple sample preparation procedures. The bound analytes were easily eluted with a solution of 30% methanol in water. It was further demonstrated that metabolites of imidazolinone compounds which retain the imidazolinone ring structure can be purified through a simple antibody affinity chromatography procedure and be identified thereafter by mass spectrometry. A comparison of mono-and poly-clonal antibody columns indicates that the monoclonal antibody with its uniform affinity and more restricted binding epitope is better for antibody affinity chromatographies. A lower amount of matrix is bound to the monoclonal antibody column, thus producing a cleaner sample than a polyclonal antibody column.The specificity of antibodies has been utilized extensively in immunoassays where analytes can be quantified in relatively crude matrices. This property can be further harnessed in affinity chromatography. Preparation of monoclonal antibodies allows an unlimited supply of mono-specific antibodies for large scale production of affinity 0097-6156/95/0586-0235$12.00/0
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