ABSTRACT
N-Hydroxyformamide-class metalloprotease inhibitors were designed and synthesized, which have potent broad-spectrum activity versus matrix metalloproteases and TNF-alpha converting enzyme (TACE). Compound 13c possesses good oral and intravenous pharmacokinetics in the rat and dog.
Subject(s)
Enzyme Inhibitors/pharmacology , Formamides/pharmacology , Matrix Metalloproteinase Inhibitors , Metalloendopeptidases/antagonists & inhibitors , Oligopeptides/pharmacology , ADAM Proteins , ADAM17 Protein , Animals , Dogs , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacokinetics , Formamides/chemistry , Oligopeptides/chemistry , Rats , Structure-Activity RelationshipABSTRACT
A sensitive high-performance liquid chromatographic method that does not require organic extraction has been developed for the determination of propranolol levels in canine and feline plasma. Equal volumes of plasma and a mixture of methanol-acetonitrile-0.1 M sodium hydroxide (3:3:4, v/v/v) were added to a microseparation unit with a 10,000 molecular mass cut-off filter. The ultrafiltrate was analyzed by reversed-phase liquid chromatography with fluorimetric detection. The consistency of the recoveries obtained eliminated the need for an internal standard (coefficients of variation less than 4%). Linear regressions for the standard curves (2.5-100 ng/ml) gave correlation coefficients above 0.9955. The detection limit was 1 ng/ml. The assay retains high sensitivity while eliminating laborious sample preparation.
Subject(s)
Propranolol/blood , Animals , Cats , Chromatography, High Pressure Liquid/veterinary , Dogs , Male , Spectrometry, Fluorescence/veterinaryABSTRACT
A simple and sensitive high-performance liquid chromatographic method was developed for the determination of enrofloxacin and ciprofloxacin in canine serum and prostatic tissue. Sample preparation consisted of mixing canine serum with a 1:1 dilution of acetonitrile and 0.1 M sodium hydroxide followed by ultrafiltration through a 10,000 molecular mass cut-off filter. Prostatic tissue was sonicated with the same solution prior to ultrafiltration. Separation of these two quinolones in the ultrafiltrate was accomplished by ion-paired liquid chromatography using a reversed-phase analytical column eluted with an acetonitrile-methanol-water solution. Enrofloxacin and ciprofloxacin were detected by a photometric ultraviolet-visible detector set at 278.6 nm and confirmed by a photodiode array detector operating from 230 to 360 nm. The limits of detection for enrofloxacin and ciprofloxacin were 4 and 2 ng/ml, respectively.
Subject(s)
Anti-Infective Agents/metabolism , Ciprofloxacin/metabolism , Fluoroquinolones , Prostate/analysis , Quinolones , Animals , Anti-Infective Agents/blood , Chromatography, High Pressure Liquid , Ciprofloxacin/blood , Dogs , Enrofloxacin , Male , Spectrophotometry, UltravioletABSTRACT
A sensitive and selective high-performance liquid chromatographic assay was developed to quantitate doxycycline concentrations in bovine tissues and body fluids. The method involved sonication of doxycycline-spiked minced tissues with appropriate solutions to extract tissue-bound drug. Acetonitrile:85% phosphoric acid:water (20:2:78) was added to doxycycline-spiked serum or urine. The mixtures were ultrafiltered through 30,000 or 10,000 Da molecular weight cutoff microseparation systems. Separation was obtained by a reversed-phase microbore column. Absorbance of the column effluent was measured by an ultraviolet-visible photodiode array detector scanning from 235 to 380 nm and/or a photometric detector operated at 268 or 345 nm. Chromatographic peak homogeneity was evaluated by three-dimensional spectrochromatograms, contour maps, and absorbance ratios.
Subject(s)
Doxycycline/analysis , Animals , Cattle , Chromatography, High Pressure Liquid , Doxycycline/blood , Doxycycline/urine , Indicators and Reagents , Kidney Medulla/analysis , Liver/analysis , Muscles/analysis , Spectrophotometry, UltravioletABSTRACT
A simple and sensitive high-performance liquid chromatographic (HPLC) method is developed for the determination of chloramphenicol (CAP) concentrations in equine, canine, and feline serum. Serum samples are diluted, then ultrafiltered using a microconcentrator with a 30,000 MW cutoff filter. CAP is separated and quantitated directly from the ultrafiltrate on a reversed-phase column using a buffered methanol mobile phase and a variable wavelength UV detector set at 278 nm. The recovery of CAP from 5 micrograms/mL spiked serum samples is determined using 10 serum samples from each of the three species. This method of sample preparation yields recoveries of 99.8%, 92.0%, and 88.6% with coefficients of variation of 1.2%, 1.3%, and 1.0% in equine, canine, and feline sera, respectively. Concentrations of CAP between 0.5 and 400 micrograms/mL as determined by peak area are found to have a linear relationship (correlation coefficient = 0.99997, n = 10), although amounts as low as 0.025 microgram/mL can be detected.
Subject(s)
Chloramphenicol/blood , Animals , Cats , Chromatography, High Pressure Liquid , Dogs , Electrochemistry , Horses , Indicators and Reagents , Photometry , Spectrophotometry, UltravioletABSTRACT
The activities of the initial enzymes of glycerolipid synthesis were inhibited by the antifertility drug gossypol acetate. Both the dihydroxyacetone phosphate acyltransferase and glycerol phosphate acyltransferase activities of microsomes isolated from liver were inhibited 60% or greater at a concentration of 60 uM. The activity of the peroxisomal dihydroxyacetone phosphate acyltransferase of liver was not greatly affected by gossypol until the peroxisomal activity was solubilized by detergent. It is suggested that gossypol can alter the capacity for glycerolipid synthesis within the microsomal and peroxisomal compartments.
